Introducer systems for bone access

ABSTRACT

Described herein are various implementations of systems and methods for accessing and modulating tissue (for example, systems and methods for accessing and ablating nerves or other tissue within or surrounding a vertebral body to treat chronic lower back pain). Assessment of vertebral endplate degeneration or defects (e.g., pre-Modic changes) to facilitate identification of treatment sites and protocols are also provided in several embodiments. Several embodiments comprise the use of biomarkers to confirm or otherwise assess ablation, pain relief, efficacy of treatment, etc. Some embodiments include robotic elements for, as an example, facilitating robotically controlled access, navigation, imaging, and/or treatment.

RELATED APPLICATIONS

This application is a continuation of International PCT Application No.PCT/US2020/050249 filed Sep. 10, 2020, which claims the benefit ofpriority to U.S. Provisional Application No. 62/899,622 filed Sep. 12,2019, the entire content of each of which is hereby incorporated byreference herein.

FIELD

Described herein are various implementations of systems and methods formodulating tissue (for example, systems and methods for ablating nervesor other tissue within or surrounding a vertebral body to treat chroniclower back pain). Several embodiments comprise the use of biomarkers toconfirm or otherwise assess ablation, pain relief, efficacy oftreatment, etc. Some embodiments include robotic elements for, as anexample, facilitating robotically controlled access, navigation,imaging, and/or treatment. Assessment of vertebral endplate degenerationor defects (e.g., pre-Modic changes) to facilitate identification oftreatment sites and protocols are also provided in several embodiments.Systems or kits of access tools for accessing target treatment locationswithin vertebral bodies are also provided.

BACKGROUND

Back pain is a very common health problem worldwide and is a major causefor work-related disability benefits and compensation. At any giventime, low back pain impacts nearly 30% of the US population, leading to62 million annual visits to hospitals, emergency departments, outpatientclinics, and physician offices. Back pain may arise from strainedmuscles, ligaments, or tendons in the back and/or structural problemswith bones or spinal discs. The back pain may be acute or chronic.Existing treatments for chronic back pain vary widely and includephysical therapy and exercise, chiropractic treatments, injections,rest, pharmacological therapy such as opioids, pain relievers oranti-inflammatory medications, and surgical intervention such asvertebral fusion, discectomy (e.g., total disc replacement), or discrepair. Existing treatments can be costly, addictive, temporary,ineffective, and/or can increase the pain or require long recoverytimes. In addition, existing treatments do not provide adequate relieffor the majority of patients and only a small percentage are surgicallyeligible.

SUMMARY

Applicant's existing technology (the Intracept® procedure by Relievant®)offers a safe and effective minimally invasive procedure that targetsthe basivertebral nerve for the relief of chronic vertebrogenic low backpain. As disclosed herein, several embodiments provide bone accesstools, additional modalities of relief for patients and/or adjuncttechnologies.

In accordance with several embodiments, quantitative efficacy oftreatment or efficacy of nerve ablation may be performed by assessinglevels of one or more biomarkers (e.g., biomarkers associated with pain,inflammation, or neurotransmission). Such assessment may be particularuseful to assess pain, for example. Pain can be very subjective based onindividual patient pain tolerance and perception. Accordingly, it can bedifficult to assess or quantify efficacy of pain treatment based onpatient feedback. It has also been difficult historically to assessefficacy of nerve ablation in real time. For example, patients may beunder anesthetic and unable to provide feedback. In other cases,patients may be awake but unable to accurately assess pain. The use ofbiomarkers, in some embodiments can facilitate pain assessment orconfirmation of efficacy of nerve ablation.

For example, a level or activity of one or more biomarkers may bemeasured or otherwise obtained prior to performing a procedure and afterperforming a procedure. The pre-procedure and post-procedure levels maybe compared in order to quantitatively (non-subjectively) assessefficacy. The biomarkers may be associated with pain levels orassociated with lesion formation (e.g., efficacy of neurotransmission orneural communication). The assessment of the level of the one or morebiomarkers may advantageously be performed in a non-invasive orminimally-invasive (e.g., non-surgical) manner in accordance withseveral embodiments. Biomarkers may also be used to assess whether aparticular subject is likely to be a candidate for nerve ablationtreatment for treatment of back pain. For example, the biomarkers may beindicative of pre-Modic changes or symptoms likely to result in Modicchanges or endplate damage (e.g., inflammation, edema, bone marrowlesions or fibrosis). The assessment of biomarker levels may indicatewhich vertebral bodies of a particular subject are candidates fortreatment to prevent (or reduce the likelihood of) back pain fromdeveloping or worsening or to treat existing back pain. Thepre-procedure biomarker assessment may also be combined withpre-procedure imaging. Mechanisms other than using biomarkers may alsobe used (in addition or in the alternative) to assess lesion formation(e.g., infrared sensing, heat markers, neurotransmission assessments viastimulation, and/or ultrasound imaging).

In some embodiments, automated systems for accessing and/or treatingtissue (such as nerves) are provided. In accordance with severalembodiments, robotically-enabled or robotically-controlled surgical,access, and/or treatment tools may provide a high level of control andprecision of movement and increased dexterity and range of motion,thereby providing increased assurance that injury will not occur totissue not desired to be impacted. Robotically-controlled tools andtechniques (e.g., computer-aided tools and techniques that mayincorporate artificial intelligence learning and feedback) may also beused to facilitate navigation to, and surgical operation at, desiredtarget treatment regions that may be difficult to access manually,thereby providing enhanced flexibility and possibilities thought not tobe possible via manual human surgery. Robotically-controlled tools andtechniques (e.g., computer-aided tools and techniques that mayincorporate artificial intelligence learning and feedback) may furtherbe used to facilitate capture of images pre-operatively orintra-operatively without exposing the target treatment regions toradiation or without requiring large incisions to be made. Nervedetection devices (e.g., nerve monitoring devices or nerve finders) mayalso be used to detect nerves along access routes that are desired to beavoided during access. Robotic or automated tools and techniques mayreduce numbers of and sizes of incisions (and therefore scars), mayreduce blood loss, may reduce pain, and may decrease recovery time.

Because the target treatment regions within vertebral bodies may befairly small in size, it may be desirable to control or adjust lesionformation so as to exhibit specific lesion shapes (e.g., football-shape,oval, elliptical, disc-shaped, cigar-shaped, dumbbell-shaped,UFO-shaped, rounded, rectangular, amorphous, etc.). Creating specificlesion shapes may allow clinicians to efficiently ablate a basivertebralnerve trunk within specific vertebral bodies (e.g., cervical, thoracic,lumbar, sacral vertebrae). The specific lesion shapes may provideincreased confidence in the efficacy of ablation while limiting theextent of thermal injury within the vertebral body. The lesion shapesmay be controlled by applying voltage differentials between differentpairs of electrodes on the same energy delivery probe or on differentenergy delivery probes for different durations. The lesion formation maybe monitored and controlled in real time (e.g., using feedback based onimaging, thermal sensing, and/or artificial intelligence) to furtherincrease confidence and efficiency. Use of two probes and deliveringenergy between the two probes may result in synergistic lesion formation(e.g., larger lesions than could be formed by individual probes alone).

Treatment procedures may include modulation of nerves within orsurrounding bones. The terms “modulation” or “neuromodulation”, as usedherein, shall be given their ordinary meaning and shall also includeablation, permanent denervation, temporary denervation, disruption,blocking, inhibition, electroporation, therapeutic stimulation,diagnostic stimulation, inhibition, necrosis, desensitization, or othereffect on tissue. Neuromodulation shall refer to modulation of a nerve(structurally and/or functionally) and/or neurotransmission. Modulationis not necessarily limited to nerves and may include effects on othertissue, such as tumors or other soft tissue.

In accordance with several embodiments, a method of ablating abasivertebral nerve within a vertebral body of a subject and confirmingefficacy of ablation of the basivertebral nerve includes obtaining afirst reading (e.g., baseline reading) of a level of a biomarker fromthe subject. The method further includes performing a denervationprocedure on the subject. As one example, the denervation procedureincludes denervating the basivertebral nerve within the vertebral body.The method also includes obtaining a second reading (e.g.,post-procedure reading) of the level of the biomarker from the subjectand determining an effect of the denervation procedure by comparing thesecond reading to the first reading to assess efficacy of thedenervation procedure.

The biomarkers may include one or more of: an inflammatory cytokine(e.g., interleukins, interferons, tumor necrosis factors,prostaglandins, and chemokines), pain indicators (e.g., substance P,calcitonin gene-related peptides (CGRPs)), an edema factor, and/or otherinflammatory factor. The first reading (e.g., baseline reading) and thesecond reading (e.g., post-procedure reading) may be obtained fromcerebrospinal fluid adjacent the vertebral body of the subject, from ablood draw (e.g., at a location within or adjacent the vertebral body ofthe subject or at a remote location systemically), from a urine sample,or other source. The biomarkers may be circulating inflammatory cells(e.g., cytokines). The biomarkers may be obtained via one or moreimmunoassay techniques (e.g., ELISAs, cytokine bead arrays, cytokinemicroarrays, flow cytometry, immunohistochemical assays, and/or thelike).

The step of denervating the basivertebral nerve within the vertebralbody may include applying energy (e.g., radiofrequency energy,ultrasound energy, microwave energy) to a target treatment region withinthe vertebral body sufficient to denervate (e.g., ablate, electroporate,molecularly dissociate, necrose) the basivertebral nerve using aradiofrequency energy delivery device. The step of denervating mayalternatively or additionally include applying an ablative fluid (e.g.,steam, chemical, cryoablative fluid) to a target treatment region withinthe vertebral body. In some implementations, the step of denervating mayinclude delivering a water jet at a pressure sufficient to denervate thenerve (e.g., between 5 and 10 MPa, between 10 and 15 MPa, between 15 and30 MPa, between 30 and 50 MPa, overlapping ranges thereof, pressuregreater than 50 MPa, or any value within the recited ranges).

In accordance with several embodiments, a method of detecting andtreating back pain of a subject includes obtaining images of a vertebralbody of the subject, analyzing the images to determine whether thevertebral body exhibits one or more symptoms associated with a pre-Modicchange, and ablating a basivertebral nerve within the vertebral body ifit is determined that the vertebral body exhibits one or more symptomsassociated with a pre-Modic change. The one or more symptoms associatedwith a pre-Modic change may include edema, inflammation, and/or tissuechanges (e.g., tissue lesions, fibrosis, or other changes in tissue typeor characteristics) of bone, bone marrow, and/or endplate(s).

In accordance with several embodiments, a method of treating a vertebralbody includes inserting a first access assembly into a first targetlocation of the vertebral body. The first access assembly includes afirst cannula and a first stylet configured to be inserted within thefirst cannula until a distal tip of the first stylet is advanced to orbeyond an open distal tip of the first cannula. The method furtherincludes removing the first stylet from the first cannula. The methodalso includes inserting a second access assembly into a second targetlocation of the vertebral body. The second access assembly including asecond cannula and a second stylet configured to be inserted within thesecond cannula until a distal tip of the second stylet is advanced to orbeyond an open distal tip of the second cannula. The method furtherincludes removing the second stylet. The method also includes insertinga first radiofrequency energy delivery device through the first cannulaand inserting a second radiofrequency energy delivery device through thesecond cannula. The first radiofrequency energy delivery device and thesecond radiofrequency energy delivery device each include at least twoelectrodes (e.g., an active electrode and a return electrode configuredto act as a bipolar electrode pair). The method further includespositioning the at least two electrodes of the first radiofrequencyenergy delivery device within the vertebral body and positioning the atleast two electrodes of the second radiofrequency energy delivery devicewithin the vertebral body.

The method also includes applying power to the first and secondradiofrequency energy delivery devices sufficient to create a desiredlesion shape within the vertebral body sufficient to ablate abasivertebral nerve within the vertebral body (e.g., football-shapedlesion, an elliptical-shaped lesion having a length-to-width ration ofat least 2:1, a cross-shaped lesion, an X-shaped lesion, a cigar-shapedlesion). The lesion may have a maximum width of 20 mm and a maximumlength of 30 mm. The lesion may have a maximum width of 70-80% of theanteroposterior depth of the vertebral body and a maximum length of70-85% of the transverse width of the vertebral body. In someimplementations, the step of applying power to the first and secondradiofrequency energy delivery devices includes independently applyingpower to the first and second radiofrequency energy delivery devices fora first duration of time (e.g., 1 minute-2 minutes, 30 seconds-90seconds, 2-5 minutes, 5-10 minutes, 10-15 minutes, overlapping rangesthereof, or any value within the recited ranges). In someimplementations, the step of applying power to the first and secondradiofrequency energy delivery devices further includes applying avoltage differential between at least one of the at least two electrodesof the first radiofrequency energy delivery device and at least one ofthe at least two electrodes of the second radiofrequency energy deliverydevice for a second duration of time (e.g., 1 minute-2 minutes, 30seconds-90 seconds, 2-5 minutes, 5-10 minutes, 10-15 minutes,overlapping ranges thereof, or any value within the recited ranges). Thefirst duration of time and the second duration of time may be the sameor different.

In accordance with several embodiments, a method of ablating abasivertebral nerve within a vertebral body includes inserting an accessassembly within a vertebral body using a robotically-controlled system.The access assembly includes at least one cannula. The method furtherincludes inserting a radiofrequency energy delivery device through thecannula to a target treatment site within the vertebral body using therobotically-controlled system, and applying power to the targettreatment site using the radiofrequency energy delivery devicesufficient to ablate the basivertebral nerve.

In some implementations, the robotically-controlled system includes oneor more robotic arms and an operator control console including at leastone processor. The system may include one or more imaging devicesconfigured to provide feedback (e.g., based on artificial intelligenceprocessing algorithms) to the robotically-controlled system to controlinsertion of the access assembly and/or the radiofrequency energydelivery device.

In accordance with several embodiments, a radiofrequency (“RF”)generator for facilitating nerve ablation includes a display screen(e.g., color active matrix display) and an instrument connection portconfigured to receive a corresponding connector of a radiofrequencyprobe. The generator further includes a first indicator light ring(e.g., circular LED indicator light ring) surrounding the instrumentconnection port that is configured to illuminate when a treatment deviceis connected to the instrument connection port. The first indicatorlight ring is configured to continuously illuminate in a solid color(e.g., white, green, blue) when the treatment device is connected to theinstrument connection port, to flash at a first pulsing rate (e.g., 1Hz) to prompt a clinician to connect the treatment device to theinstrument connection port, and to flash at a second pulsing ratedifferent than (e.g., greater than 1 Hz, such as 2 Hz, 3 Hz or 4 Hz) thefirst pulsing rate to indicate an error condition. The generator mayoptionally be configured to output an audible alert or alarm to indicatethe error condition. The generator also includes an energy deliveryactuation button configured to be pressed by an operator to start andstop delivery of radiofrequency energy and a second indicator light ring(e.g., circular LED light ring) surrounding the actuation button. Thesecond indicator light ring is configured to continuously illuminate ina solid color (e.g., white, blue, green) when the generator is poweredon and ready to initiate energy delivery, to flash at a third pulsingrate (e.g., 1 Hz) to prompt the operator to press the actuation buttonto initiate energy delivery, and to flash at a fourth pulsing ratedifferent than (e.g., greater than 1 Hz, such as 2 Hz, 3 Hz, 4 Hz) thethird pulsing rate when energy delivery has been paused or stopped.

In accordance with several embodiments, a system for facilitating nerveablation includes an operator control console comprising acomputer-based control system including at least one processor that isconfigured to execute program instructions stored on a non-transitorycomputer-readable medium to carry out a nerve ablation procedure toablate a basivertebral nerve within one or more vertebral bodies usingautomated robotic surgical arms. The one or more robotic surgical armsare configured to move with six or more degrees of freedom and tosupport or carry access tools (e.g., cannulas, stylets, bone drills,curettes), treatment devices (e.g., radiofrequency probes, microwaveablation catheters, ultrasound probes), and/or diagnostic devices (e.g.,cameras, sensors, and/or the like). The system may optionally includeone or more imaging devices configured to obtain images of a targettreatment site prior to, during, and/or after a treatment procedure.

In accordance with several embodiments, a method of facilitatingablation of a basivertebral nerve within a vertebral body comprisingapplying radiofrequency energy to a location within the vertebral bodyaccording to the following treatment parameters: a frequency between 400kHz and 600 kHz (e.g., between 400 kHz and 500 kHz, between 450 kHz and500 kHz, between 470 kHz and 490 kHz, between 500 kHz and 600 kHz,overlapping ranges thereof, or any value within the recited ranges); atarget temperature of between 80 degrees Celsius and 90 degrees Celsius(e.g., 80 degrees Celsius, 85 degrees Celsius, 90 degrees Celsius); atemperature ramp of between 0.5 and 3 degrees Celsius per second (e.g.,0.5 degree Celsius per second, 1 degree Celsius per second, 1.5 degreesCelsius per second, 2 degrees Celsius per second, 2.5 degrees Celsiusper second, 3 degrees Celsius per second); and an active energy deliverytime of between 10 minutes and 20 minutes (e.g., 10 minutes, 12,minutes, 14 minutes, 15 minutes, 16 minutes, 18 minutes, 20 minutes). Insome implementations, a target ablation zone has a major diameter alonga long axis of between 20 mm and 30 mm and a minor diameter along ashort axis of between 5 mm and 15 mm.

In accordance with several embodiments, a kit for facilitating nerveablation includes one or more biological assays configured to determineat least one biological marker (e.g., cytokine, substance P or otherindicator of pain, heat shock protein). The determination includes atleast one of a binary detection of a presence of the at least onebiological marker, and/or a quantification (e.g., total amount) of theat least one biological marker. The determination may also optionallyinclude an indication of location of any of the at least one biomarkeror a location of a highest concentration of the at least one biomarker.

The kit may optionally include one or more access tools (e.g., stylets,cannulas, curettes, bone drills) configured to access a target nerve tobe treated (e.g., basivertebral nerve). The kit may also oralternatively optionally include one or more treatment tools configuredto modulate (e.g., ablate, stimulate, denervate, inhibit, necrose,electroporate, molecularly dissociate) the target nerve. The optionaltreatment tool include one or a combination of the following: aradiofrequency energy delivery device, a microwave energy deliverydevice, an ultrasound energy delivery device, a cryomodulation device(e.g., cryoablation device), a laser energy delivery device, and/or adrug eluting device (e.g., chemical or fluid ablation device configuredto elute a fluid capable of denervating or ablating a nerve, such asalcohol or phenol).

In accordance with several embodiments, a method of detecting andtreating back pain of a subject includes obtaining images of a vertebralbody of the subject and analyzing the images to determine whether thevertebral body exhibits one or more symptoms associated with a pre-Modicchange. The method also includes modulating (e.g., ablating,denervating, stimulating) an intraosseous nerve (e.g., basivertebralnerve) within the vertebral body if it is determined that the vertebralbody exhibits one or more symptoms associated with a pre-Modic change.

The images may be obtained, for example, using an MRI imaging modality,a CT imaging modality, an X-ray imaging modality, an ultrasound imagingmodality, or fluoroscopy. The one or more symptoms associated with apre-Modic change may comprise characteristics likely to result in Modicchanges (e.g., Type 1 Modic changes, Type 2 Modic changes). The one ormore symptoms associated with a pre-Modic change may comprise initialindications or precursors of edema or inflammation at a vertebralendplate prior to a formal characterization or diagnosis as a Modicchange. The one or more symptoms may include edema, inflammation, and/ortissue change within the vertebral body or along a portion of avertebral endplate of the vertebral body. Tissue changes may includetissue lesions or changes in tissue type or characteristics of anendplate of the vertebral body and/or tissue lesions or changes intissue type or characteristics of bone marrow of the vertebral body. Theone or more symptoms may include focal defects, erosive defects, rimdefects, and corner defects of a vertebral endplate of the vertebralbody.

The thermal treatment dose applied may include delivery of one or moreof radiofrequency energy, ultrasound energy, microwave energy, and laserenergy. Ablating the basivertebral nerve within the vertebral body maycomprise applying a thermal treatment dose to a location within thevertebral body of at least 240 cumulative equivalent minutes (“CEM”)using a CEM at 43 degrees Celsius model. In some embodiments, thethermal treatment dose is between 200 and 300 CEM (e.g., between 200 and240 CEM, between 230 CEM and 260 CEM, between 240 CEM and 280 CEM,between 235 CEM and 245 CEM, between 260 CEM and 300 CEM) or greaterthan a predetermined threshold (e.g., greater than 240 CEM).

In some embodiments, ablating the basivertebral nerve within thevertebral body comprises advancing at least a distal end portion of aradiofrequency energy delivery probe comprising two electrodes (e.g., abipolar probe having an active electrode and a return electrode) to atarget treatment location within the vertebral body and applyingradiofrequency energy to the location using the energy delivery probe togenerate a thermal treatment dose sufficient to modulate (e.g., ablate,denervate, stimulate) the intraosseous nerve (e.g., basivertebralnerve). The radiofrequency energy may have a frequency between 400 kHzand 600 kHz (e.g., between 400 kHz and 500 kHz, between 425 kHz and 475kHz, between 450 kHz and 500 kHz, between 450 kHz and 550 kHz, between475 kHz and 500 kHz, between 500 kHz and 600 kHz, overlapping rangesthereof, or any value within the recited ranges). In some embodiments,the thermal treatment dose is configured to achieve a target temperatureof between 70 degrees Celsius and 95 degrees Celsius (e.g., between 70degrees Celsius and 85 degrees Celsius, between 80 degrees Celsius and90 degrees Celsius, between 85 degrees Celsius and 95 degrees Celsius,overlapping ranges thereof, or any value within the recited ranges) atthe location. The thermal treatment dose may be delivered with atemperature ramp of between 0.1 and 5 degrees Celsius per second (e.g.,between 0.5 and 1.5 degrees Celsius per second, between 1 and 2 degreesCelsius per second, between 1.5 and 3 degrees Celsius per second,between 0.5 and 3 degrees Celsius per second, between 1.5 and 5 degreesCelsius per second, overlapping ranges thereof, or any value within therecited ranges. In some embodiments, the temperature ramp is greaterthan 5 degrees Celsius per second. The radiofrequency energy may beapplied for an active energy delivery time of between 5 minutes and 30minutes (e.g., between 5 minutes and 15 minutes, between 10 minutes and20 minutes, between 15 minutes and 30 minutes, overlapping rangesthereof, or any value within the recited ranges). The thermal treatmentdose may form a targeted lesion zone at the target treatment locationhaving a maximum cross-sectional dimension of less than 15 mm.

Ablating the basivertebral nerve may comprise generating a targetedablation zone formed by a lesion having a “football” or ellipticalprofile shape. Ablating the basivertebral nerve may comprise generatinga targeted ablation zone having a maximum cross-sectional dimension(e.g., diameter, height, width, length) of less than 15 mm. In someembodiments, ablating the basivertebral nerve comprises generating atargeted ablation zone having a maximum cross-sectional dimension (e.g.,major diameter) along a long axis of between 20 mm and 30 mm and amaximum cross-sectional dimension (e.g., minor diameter) along a shortaxis of between 5 mm and 15 mm.

In some embodiments, the method is performed without use of any coolingfluid. The method may further include modulating (e.g., ablating,denervating, stimulating) an intraosseous nerve (e.g., basivertebralnerve) within a second vertebral body superior to or inferior to thefirst vertebral body.

In accordance with several embodiments, a method of detecting andtreating back pain of a subject includes identifying a candidatevertebral body for treatment based on a determination that the vertebralbody exhibits one or more symptoms or defects associated with vertebralendplate degeneration and ablating a basivertebral nerve within theidentified candidate vertebral body by applying a thermal treatment doseto a location within the vertebral body of at least 240 cumulativeequivalent minutes (“CEM”) using a CEM at 43 degrees Celsius model. Theone or more symptoms associated with vertebral endplate degeneration ordefects include pre-Modic change characteristics.

In some embodiments, the determination is based on images of thecandidate vertebral body (e.g., MRI images, CT images, X-ray images,fluoroscopic images, ultrasound images). In some embodiments, thedetermination is based on obtaining biomarkers from the subject. Thebiomarkers may be obtained, for example, from one or more blood serumsamples (e.g., blood plasma). The biomarkers may be obtained over anextended period of time (e.g., a period of days, weeks, or months) or ata single instance in time.

In some embodiments, the location of the applied thermal treatment doseis in a posterior half of the vertebral body. The location may include ageometric center of the vertebral body. The location may be at least 5mm (e.g., at least 1 cm) from a posterior border (e.g., posteriorcortical aspect) of the vertebral body.

In some embodiments, the method includes advancing at least a distal endportion of a bipolar radiofrequency energy delivery probe having twoelectrodes to the location. The method may further include forming apassageway through a pedicle and into the vertebral body, then advancingat least the distal end portion of the bipolar radiofrequency energydelivery probe along the passageway to the location, and then applyingthe thermal treatment dose to the location using the bipolarradiofrequency energy delivery probe.

In some embodiments, the method further includes applying radiofrequencyenergy to a second location within a second vertebral body. The secondvertebral body may be of a vertebra of a different vertebral level thanthe first vertebral body. The second vertebral body may be of a vertebraadjacent to the first vertebral body.

In accordance with several embodiments, an introducer system adapted tofacilitate percutaneous access to a target treatment location withinbone (e.g., a vertebral body) includes an introducer cannula comprisinga proximal handle and a distal elongate hypotube extending from theproximal handle. The system further includes an introducer styletcomprising a proximal handle and a distal elongate shaft extending fromthe proximal handle. The proximal handle of the introducer includes acentral opening in its upper surface that is coupled to a lumen of thedistal elongate hypotube to facilitate insertion of the introducerstylet into the central opening and into the distal elongate hypotube ofthe introducer cannula. The proximal handle of the introducer cannulaincludes one or more slots configured to receive at least a portion ofthe proximal handle of the introducer stylet so as to facilitateengagement and alignment between the introducer stylet and theintroducer cannula. The proximal handle of the introducer styletincludes an anti-rotation tab configured to be received within one ofthe one or more slots so as to prevent rotation of the introducer styletwithin the introducer cannula. A distal end of the distal elongate shaftof the introducer stylet includes a distal cutting tip and a scallopedsection proximal to the distal cutting tip so as to provide gaps betweenan outer diameter of the distal end of the distal elongate shaft and theinner diameter of the introducer cannula.

In some embodiments, the proximal handle of the introducer styletfurther includes a press button that, when pressed: (a) disengages theanti-rotation tab and allows for rotation of the introducer styletwithin the introducer stylet, and (b) allows for removal of theintroducer stylet from the introducer cannula. The proximal handle ofthe introducer stylet may include a ramp configured to provide amechanical assist for removal of the introducer stylet from theintroducer cannula. The proximal handle of the introducer cannula maycomprise a T-shaped, or smokestack shaped, design.

The introducer system may further include a curved cannula assembly. Thecurved cannula assembly may include a cannula comprising a proximalhandle with a curved insertion slot and a distal polymeric tube. Thedistal polymeric tube may include a curved distal end portion having apreformed curvature but configured to bend when placed under constraint(e.g., constraint by insertion through a straight introducer cannula).The curved cannula assembly may further include a stylet comprising aproximal handle and a distal elongate shaft. The distal elongate shaftincludes a curved distal end portion having a preformed curvature butconfigured to bend when placed under constraint (e.g., constraint byinsertion through a cannula or bone tissue) and a distal channeling tip.A length of the curved distal end portion of the distal elongate shaftproximal to the distal channeling tip (e.g., a springboard or platformportion) may comprise a cross-section circumference profile that is lessthan a full cross-section circumference profile (e.g., cross-sectioncircumference profile of neighboring or adjacent portions of the distalelongate shaft or of the distal channeling tip), such that there is alarger gap between an outer cross-sectional dimension of the curveddistal end portion of the distal elongate shaft and the inner diameterof the curved distal end portion of the cannula along the length of thecurved distal end portion of the distal elongate shaft proximal to thedistal channeling tip. The less than full cross-section circumferenceprofile may comprise a “D” shape. The overall cross-sectioncircumference profile may thus be asymmetric (e.g., not uniform orconstant along its entire length).

The proximal handle of the stylet may include a bail mechanism comprisesa bail actuator that is adapted to cause axial movement (e.g., proximalmovement upon actuation) of the distal channeling tip of the distalelongate shaft of the stylet with respect to the cannula so as tofacilitate insertion of the curved cannula assembly through theintroducer cannula and withdrawal of the stylet of the curved cannulaassembly from the cannula of the curved cannula assembly after formationof a curved path within the bone.

The introducer system may further include an introducer drill adapted tobe introduced into and through the introducer cannula to form a furtherpath within the bone after removal of the introducer stylet from theintroducer cannula. The introducer drill may include a fluted distalportion and a distal drill tip, wherein drill flutes of the fluteddistal portion taper away (e.g., flutes go from higher volume to lowervolume) from the distal drill tip so as to facilitate improved bone chippacking within an open volume defined by the drill flutes as bone chipsare generated by operation of the introducer drill. The aforementionedsystem components may be provided as a kit with instructions for use.

In accordance with several embodiments, a system configured to providecurved access within bone includes a cannula comprising a proximalhandle with a curved insertion slot and a distal polymeric tube, withthe distal polymeric tube including a curved distal end portion having apreformed curvature but configured to bend when placed under constraint.The system further includes a stylet comprising a proximal handle and adistal elongate shaft, wherein the distal elongate shaft includes acurved distal end portion having a preformed curvature but configured tobend when placed under constraint and a distal channeling tip. A lengthof the curved distal end portion of the distal elongate shaft proximalto the distal channeling tip comprises a cross-section circumferenceprofile that is less than a full cross-section circumference profilesuch that there is a larger gap between an outer cross-sectionaldimension of the curved distal end portion of the distal elongate shaftand the inner diameter of the curved distal end portion of the cannulaalong the length of the curved distal end portion of the distal elongateshaft proximal to the distal channeling tip. In some embodiments, thecross-section circumference profile comprises a “D” shape. An uppersurface of the length of the curved distal end portion may be generallyflat. The proximal handle of the stylet may include a bail configured tobe actuated so as to cause proximal axial retraction of the stylet withrespect to the cannula when the proximal handle of the stylet is engagedwith the proximal handle of the cannula. In some embodiments, the curveddistal end portion of the distal elongate shaft is constructed such thatthe preformed curvature of the curved distal end portion does notdeviate by more than 20 degrees upon insertion within the bone. Amaximum vertical cross-sectional dimension of the length of the curveddistal end portion may be between 40% and 80% (e.g., between 40% and60%, between 45% and 70%, between 50% and 65%, between 60% and 80%,overlapping ranges thereof, or any value within the recited ranges) of amaximum cross sectional dimension of proximal and distal regions of thecurved distal end portion bordering the length of the curved distal endportion. The system components may be provided as a kit withinstructions for use.

In accordance with several embodiments, a method of accessing a targettreatment location within a vertebral body identified as having hardbone includes advancing an introducer assembly through skin adjacent thevertebral body and into a pedicle connected to the vertebral body, theintroducer assembly including an introducer stylet inserted within anintroducer cannula with a distal cutting tip of the introducer styletextending out of the introducer cannula. The method further includesremoving the introducer stylet from the introducer cannula while leavingthe introducer cannula in place. The method also includes inserting anintroducer drill through and beyond the introducer cannula and throughthe pedicle and into cancellous bone of the vertebral body. Insertingthe introducer drill includes rotating the introducer drill. Theintroducer drill includes a fluted distal portion and a distal drilltip. The drill flutes of the fluted distal portion taper away from thedistal drill tip so as to facilitate improved bone chip packing withinan open volume defined by the drill flutes as bone chips are generatedby operation of the introducer drill.

In accordance with several embodiments, inserting the introducer drillmay involve not malleting on the introducer drill. In some embodiments,inserting the introducer drill does include malleting on a proximalhandle of the introducer drill. The method may further include removingthe introducer drill from the introducer cannula. The method may alsoinclude inserting a curved cannula assembly into a curved slot of aproximal handle of the introducer cannula. The curved cannula assemblymay include a second cannula including a proximal handle with a curvedinsertion slot and a distal polymeric tube, wherein the distal polymerictube includes a curved distal end portion having a preformed curvaturebut configured to bend when placed under constraint. The curved cannulaassembly may also include a second stylet including a proximal handleand a distal elongate shaft. The distal elongate shaft of the secondstylet includes a curved distal end portion having a preformed curvaturebut configured to bend when placed under constraint and a distalchanneling tip. A length of the curved distal end portion of the distalelongate shaft proximal to the distal channeling tip may comprise across-section circumference profile that is less than a fullcross-section circumference profile such that there is a larger gapbetween an outer cross-sectional dimension of the curved distal endportion of the distal elongate shaft and the inner diameter of thecurved distal end portion of the second cannula along the length of thecurved distal end portion of the distal elongate shaft proximal to thedistal channeling tip.

In some embodiments, the method further includes removing the secondstylet from the second cannula. The method may also include inserting athird stylet into a slot of the proximal handle of the second cannulaand beyond an open distal tip of the second cannula, wherein the thirdstylet is configured to form a straight path (e.g., beyond a curved pathformed by the curved cannula assembly) starting from the open distal tipof the second cannula toward the target treatment location, and removingthe third stylet from the second cannula after formation of the straightpath. The method may include inserting a treatment device into the slotof the proximal handle of the second cannula and beyond the open distaltip of the second cannula to the target treatment location andperforming therapy at the target treatment location using the treatmentdevice. The therapy may include ablating at least 75% of the branches ofa basivertebral nerve within the bone (e.g., vertebral body).

Several embodiments of the invention have one or more of the followingadvantages: (i) increased treatment accuracy; (ii) increased efficacyand enhanced safety; (iii) increased efficiency; (iv) increasedprecision; (v) synergistic results; (vi) “one-and-done” procedure thatdoes not require further surgical intervention; (vii) treatment ofchronic low back pain; (viii) prevention of pain due to early detectionof factors likely to cause pain in the future; (ix) reduction ofunwanted stoppages or interruptions in treatment procedure (x) ease ofuse (e.g., due to reduced friction or force).

For purposes of summarizing the disclosure, certain aspects, advantages,and novel features of embodiments of the disclosure have been describedherein. It is to be understood that not necessarily all such advantagesmay be achieved in accordance with any particular embodiment of thedisclosure provided herein. Thus, the embodiments disclosed herein maybe embodied or carried out in a manner that achieves or optimizes oneadvantage or group of advantages as taught or suggested herein withoutnecessarily achieving other advantages as may be taught or suggestedherein.

The methods summarized above and set forth in further detail belowdescribe certain actions taken by a practitioner; however, it should beunderstood that they can also include the instruction of those actionsby another party. Thus, actions such as “For example, actions such as“applying thermal energy” include “instructing the applying of thermalenergy.” Further aspects of embodiments of the disclosure will bediscussed in the following portions of the specification. With respectto the drawings, elements from one figure may be combined with elementsfrom the other figures.

BRIEF DESCRIPTION OF THE DRAWINGS

Several embodiments of the disclosure will be more fully understood byreference to the following drawings which are for illustrative purposesonly:

FIG. 1 illustrates various vertebral levels and vertebrae that may betreated by the systems and methods described herein.

FIG. 2 illustrates pelvic bones of a human to illustrate potentialmethods of accessing certain vertebral bodies.

FIG. 3 illustrates an example kit or system of access tools configuredto access a vertebral body.

FIGS. 3A-3C include various views of an introducer cannula of the kit orsystem of FIG. 3.

FIG. 3D is a side view of an introducer stylet of the kit or system ofFIG. 3 and FIG. 3E is a side view of a distal cutting tip of anintroducer stylet.

FIGS. 3F-3H illustrate a proximal portion of an introducer assembly ofthe kit or system of FIG. 3.

FIG. 3I is a side view and FIG. 3J is a top view of a curved cannula ofthe kit or system of FIG. 3.

FIG. 3K is a side view of a J-stylet of the kit or system of FIG. 3 andFIGS. 3L and 3M show a side view and a perspective view of a curveddistal end portion of the J-stylet of FIG. 3K.

FIGS. 3N and 3O illustrate insertion of the J-stylet of FIGS. 3K-3M intothe curved cannula of FIGS. 3I and 3J.

FIG. 3P illustrates insertion of the curved cannula assembly of the kitor system of FIG. 3 into the introducer cannula of FIGS. 3A-3C. FIG. 3Qis a side cross-section view of a proximal portion of the introducercannula and the curved distal end portions of the curved cannulaassembly.

FIGS. 3R and 3S illustrate operation of a gear wheel of the curvedcannula of FIGS. 3I and 3J in connection with insertion of the curvedcannula assembly into the introducer cannula. FIGS. 3T and 3U illustrateoperation of a bail of the J-stylet of FIGS. 3K-3M to facilitateinsertion and retraction of the J-stylet from the curved cannula.

FIG. 3V is a side view of a straight stylet of the kit or system of FIG.3 and FIG. 3W is side cross-section view of a distal end portion of thestraight stylet.

FIGS. 3X-3Z illustrate an optional introducer drill of the kit or systemof FIG. 3. FIG. 3Z illustrates the introducer drill inserted fullywithin the introducer cannula.

FIGS. 3AA-3HH illustrate various steps of a method of accessing andtreating tissue within a vertebral body using one or more of the accesstools of the kit or system of FIG. 3.

FIG. 4 illustrates an example radiofrequency generator.

FIG. 5A-5D illustrate example lesion shapes configured to be formed toablate intraosseous nerves within bone (e.g., vertebral body).

FIG. 6 illustrates an example of a system including two probes and twointroducer assemblies configured to facilitate formation of a desiredlesion.

FIG. 7 illustrates a schematic block diagram of a robotically-enabledsystem.

DETAILED DESCRIPTION

Several implementations described herein are directed to systems andmethods for modulating nerves within or adjacent (e.g., surrounding)bone. In some implementations, an intraosseous nerve (e.g.,basivertebral nerve) within a bone (e.g., vertebral body) of the spineis modulated for treatment, or prevention of, chronic back pain. Thevertebral body may be located in any level of the vertebral column(e.g., cervical, thoracic, lumbar and/or sacral). FIG. 1 schematicallyillustrates a vertebral column and the various vertebral segments orlevels. Multiple vertebral bodies may be treated in a single visit orprocedure (simultaneously or sequentially). The multiple vertebralbodies may be located in a single spine segment (e.g., two adjacentvertebral bodies in the sacral spine segment (e.g., S1 and S2) or lumbarspine segment (e.g., L3, L4 and/or L5) or thoracic spine segment orcervical spine segment) or in different spine segments (e.g., an L5vertebra in the lumbar spine segment and an S1 vertebra in the sacralspine segment). Intraosseous nerves within bones other than vertebralbodies may also be modulated. For example, nerves within a humerus,radius, femur, tibia, calcaneus, tarsal bones, hips, knees, and/orphalanges may be modulated.

In some implementations, the one or more nerves being modulated areextraosseous nerves located outside the vertebral body or other bone(e.g., at locations before the nerves enter into, or after they exitfrom, a foramen of the bone). Other tissue in addition to, oralternative to, nerves may also be treated or otherwise affected (e.g.,tumors or other cancerous tissue or fractured bones). Portions of nerveswithin or on one or more vertebral endplates or intervertebral discsbetween adjacent vertebral bodies may be modulated.

The modulation of nerves or other tissue may be performed to treat oneor more indications, including but not limited to chronic low back pain,upper back pain, acute back pain, joint pain, tumors in the bone, and/orbone fractures. The modulation of nerves may also be performed inconjunction with bone fusion or arthrodesis procedures so as to providesynergistic effects or complete all-in-one, “one-and-done” treatmentthat will not require further surgical or minimally invasiveinterventions.

In some implementations, fractures within the bone may be treated inaddition to denervation treatment and/or ablation of tumors by applyingheat or energy and/or delivering agents or bone filler material to thebone. For example, bone morphogenetic proteins and/or bone cement may bedelivered in conjunction with vertebroplasty or other procedures totreat fractures or promote bone growth or bone healing. In someimplementations, energy is applied and then agents and/or bone fillermaterial is delivered in a combined procedure. In some aspects,vertebral compression fractures (which may be caused by osteoporosis orcancer) are treated in conjunction with energy delivery to modulatenerves and/or cancerous tissue to treat back pain.

In accordance with several implementations, the systems and methods oftreating back pain or facilitating neuromodulation of intraosseousnerves described herein can be performed without surgical resection,without general anesthesia, without cooling (e.g., without coolingfluid), and/or with virtually no blood loss. In some embodiments, thesystems and methods of treating back pain or facilitatingneuromodulation of intraosseous nerves described herein facilitate easyretreatment if necessary. In accordance with several implementations,successful treatment can be performed in challenging ordifficult-to-access locations and access can be varied depending on bonestructure or differing bone anatomy. One or more of these advantagesalso apply to treatment of tissue outside of the spine (e.g., otherorthopedic applications or other tissue).

Access to the Vertebral Body

Methods of Access

Various methods of access may be used to access a vertebral body orother bone. In some implementations, the vertebral body is accessedtranspedicularly (through one or both pedicles). In otherimplementations, the vertebral body is accessed extrapedicularly (e.g.,without traversing through a pedicle). In some implementations, thevertebral body is accessed using an extreme lateral approach or atransforaminal approach, such as used in XLIF and TLIF interbody fusionprocedures. In some implementations, an anterior approach is used toaccess the vertebral body.

Certain vertebrae in the sacral or lumbar levels (e.g., S1 vertebra, L5vertebra) may also be accessed generally posterolaterally using atrans-ilium approach (e.g., an approach through an ilium bone). Withreference to FIG. 2, an access hole may be formed through the ilium at alocation designed to facilitate access to the vertebral body or bodiesin the sacral or lumbar region. For example, access tools (e.g., anintroducer assembly including a cannula/stylet combination) may bedelivered through an ilium and/or sacroiliac joint or sacral ala into anS1 vertebra under image guidance (e.g., CT image guidance and/orfluoroscopy) and/or using stereotactic or robotic-assisted surgicaland/or navigation systems, such as the robotic system described inconnection with FIG. 7. A treatment device could then be insertedthrough an introducer and/or other access cannula of the access tools toa target treatment location within a sacral or lumbar vertebra. Atrans-ilium approach may advantageously increase the ability of theclinician to access the target treatment location in a particularportion or region of the vertebral body (e.g., posterior portion orregion) that is not capable of being adequately accessed using atranspedicular approach. In some implementations, the vertebral body maybe accessed directly through the cerebrospinal fluid and through thedura into a posterior region of the vertebral body.

In some implementations, the vertebral body may be accessedtransforaminally through a basivertebral foramen. Transforaminal accessvia the spinal canal may involve insertion of a “nerve finder” or nervelocator device and/or imaging/diagnostic tool to avoid damaging spinalcord nerves upon entry by the access tools or treatment devices. Thenerve locator device may comprise a hand-held stimulation system such asthe Checkpoint Stimulator and Locator provided by Checkpoint Surgical®or the EZstim® peripheral nerve stimulator/nerve locators provided byAvanos Medical, Inc. The nerve finder or nerve locator device couldadvantageously identify sensitive nerves that should be avoided by theaccess tools so as not to risk paralysis or spinal cord injury uponaccessing the target treatment site. The nerve locator device may beconfigured to apply stimulation signals between two points or locationsand then assess response to determine presence of nerves in the areabetween the two points or locations. The nerve locator device mayinclude a bipolar pair of stimulation electrodes or monopolarelectrodes. In some implementations, the nerve locator features may beimplemented on the access tools or treatment devices themselves asopposed to a separate stand-alone device.

Access Tools and Treatment Devices

Access tools may include an introducer assembly including an outercannula and a sharpened stylet, an inner cannula configured to beintroduced through the outer cannula, and/or one or more additionalstylets, curettes, or drills to facilitate access to an intraosseouslocation within a vertebral body or other bone. The access tools (e.g.,outer cannula, inner cannula, stylets, curettes, drills) may havepre-curved distal end portions or may be actively steerable orcurveable. Any of the access tools may have beveled or otherwise sharptips or they may have blunt or rounded, atraumatic distal tips. Curveddrills may be used to facilitate formation of curved access paths withinbone. Any of the access tools may be advanced over a guidewire in someimplementations.

The access tools may be formed of a variety of flexible materials (e.g.,ethylene vinyl acetate, polyethylene, polyethylene-based polyolefinelastomers, polyetheretherketone, polypropylene, polypropylene-basedelastomers, styrene butadiene copolymers, thermoplastic polyesterelastomers, thermoplastic polyurethane elastomers, thermoplasticvulcanizate polymers, metallic alloy materials such as nitinol, and/orthe like). Combinations of two or more of these materials may also beused. The access tools may include chevron designs or patterns or slitsalong the distal end portions to increase flexibility or bendability.Any of the access tools may be manually or automatically rotated (e.g.,using a robotic control system such as described in connection with FIG.7) to facilitate a desired trajectory.

In some implementations, an outer cannula assembly (e.g., introducerassembly) includes a straight outer cannula and a straight styletconfigured to be received within the outer cannula. The outer cannulaassembly may be inserted first to penetrate an outer cortical shell of abone and provide a conduit for further access tools to the innercancellous bone. An inner cannula assembly may include a cannula havinga pre-curved or steerable distal end portion and a stylet having acorresponding pre-curved or steerable distal end portion. Multiplestylets having distal end portions with different curvatures may beprovided in a kit and selected from by a clinician. The inner cannulaassembly may alternatively be configured to remain straight andnon-curved.

With reference to FIG. 3, in one implementation, a kit or system ofaccess tools includes an introducer assembly 110 comprised of anintroducer cannula 112 and an introducer stylet 114, a curved cannulaassembly 210 comprised of a curved cannula 212 and a J-stylet 214, and astraight stylet 314. The introducer stylet 114 may be bevel tipped,trocar tipped, and/or diamond tipped. The introducer stylet 114 isconfigured to be received in a lumen of the introducer cannula 112 in amanner such that a distal tip of the introducer stylet 114 protrudesfrom an open distal tip of the introducer cannula 112, thereby formingthe introducer assembly 110 in combination. The J-stylet 214 isconfigured to be received in a lumen of the curved cannula 212 in amanner such that a distal tip of the J-stylet 214 protrudes from an opendistal tip of the curved cannula 212, thereby forming the curved cannulaassembly 210 in combination. The curved cannula 212 and the J-stylet 214may each comprise a straight proximal main body portion and a curveddistal end portion. The curves of the curved distal end portions of thecurved cannula 212 and the J-stylet 214 may correspond to each other.The straight stylet 314 is a flexible channeling stylet configured to bedelivered through the curved cannula 212 and then to form and maintain astraight or generally straight path upon exiting the open distal tip ofthe curved cannula 212.

The access tools may be provided as a kit that may optionallyadditionally include one or more additional introducer cannulas, one ormore additional introducer stylets (e.g., with different tips, such asone with a bevel tip and one with a diamond or trocar tip), one or twoor more than two additional curved cannulas (e.g., having a curveddistal end portion of a different curvature than a first curvedcannula), an additional J-stylet (e.g., having a different curvature ordifferent design configured to access hard bone), an introducer drill440, and/or an additional straight stylet (e.g., having a differentlength than the first straight stylet.

In some embodiments, the access tools (e.g., kit) may be specificallydesigned and adapted to facilitate access to hard, non-osteoporotic bone(e.g., bone surrounding or within a vertebral body, such as a cervicalvertebra, a thoracic vertebra, a lumbar vertebra, or a sacral vertebra).Hard bone may be determined based on bone mass density testing,compressive strength determinations, compressive modulus determinations,imaging modalities, or based on tactile feel by the operator as accessinstruments are being advanced. In some implementations, hard bone maybe determined as bone having a bone mineral density score within astandard deviation of a normal healthy young adult (e.g., a T scoregreater than or equal to −1). In some implementations, hard bone may beidentified as bone having a compressive strength of greater than 4 MPaand/or a compressive modulus of greater than 80 MPa for cancellous boneand greater than 5.5 MPa and/or a compressive modulus of greater than170 MPa for cortical bone. Some kits may include at least two of everyaccess instrument. Some kits may include optional add-on components oraccessory kit modules for accessing hard bone (e.g., the introducerdrill 440 and J-stylet 214 specially configured to access hard bone).Some kits may include optional additional access tool components oraccessory kit modules adapted to access one or more additional vertebraein the same spinal segment or in different spinal segments. The kit mayalso include one or more (e.g., at least two) treatment devices (such asradiofrequency energy delivery probes).

FIGS. 3A-3C illustrate various views of an embodiment of the introducercannula 112. The introducer cannula 112 includes a proximal handle 116and a distal hypotube 118 extending from the proximal handle 116. Theillustrated proximal handle 116 comprises a “smokestack” or “T-Handle”design configuration adapted to provide sufficient finger clearance andgripping (e.g., two fingers on each side of a lower flange 113 of theproximal handle 116 and along the lower surface of a crossbar portion115) to facilitate removal. However, alternative design configurationsfor the proximal handle other than a “smokestack” or “T-handle” designmay be incorporated.

The proximal handle 116 includes an upper central opening 120 configuredto facilitate straight axial insertion of an introducer stylet 114 orother straight access tool. The upper central opening 120 may bepositioned so as to correspond with (e.g., be coaxial with) a centrallumen extending through the hypotube 118 of the introducer cannula 112so as to facilitate insertion of straight instruments (e.g., introducerstylet 114 or steerable cannulas or steerable stylets) therethrough. Theproximal handle 116 may also include coupling features 121 (e.g.,recesses, notches, grooves, tabs) to facilitate coupling or mating of aproximal handle 216 of the introducer stylet 114 with the proximalhandle 116 of the introducer cannula 112. The coupling features 121 maybe adapted to prevent rotation of the introducer stylet 114 and/or toprovide assurance that a distal tip 125 of the introducer stylet 114extends beyond an open distal tip 122 of the hypotube 118 of theintroducer cannula 112 so as to enable penetration of the distal tip 125of the introducer stylet 114 through bone. The upper surface of theproximal handle 116 of the introducer cannula 112 also includes a curvedlateral slot 117 and curved ramp 141 to facilitate insertion of thecurved cannula assembly 210 into the proximal handle 116 and then intoand along the central lumen of the hypotube 118.

The central lumen of the hypotube 118 extends from the proximal handle116 to the open distal tip 122 of the hypotube 118. The hypotube 118 maybe flared or tapered such that the diameter of the hypotube 118 is notconstant along its entire length. For example, the diameter may decreaseabruptly at a certain distance (e.g., 1 cm-3 cm) from a lower edge ofthe lower flange 113 of the proximal handle 116 and then continue with aconstant diameter distally of an abrupt flare 119. In anotherembodiment, the diameter may decrease gradually (e.g., taper uniformly)along the length of the hypotube 118 from the start of the flare 119 tothe open distal tip 122 of the hypotube 118. The central lumen of thehypotube 118 may be coated with a medical grade silicone lubricant toimprove tool insertion and removal. The outer diameter of the hypotube118 may range from 4.2 mm to 4.5 mm.

The proximal handle 116 of the introducer cannula 112 may also includean overdrive indication mechanism configured to indicate when the curvedcannula assembly 210 has been fully deployed from the introducer cannulasuch that further advancement of the curved cannula would place thecurved cannula assembly 210 at risk of being overdriven from theintroducer cannula 112, which could result in damage to the curvedcannula assembly 210. The overdrive indication mechanism may comprisetwo slots 123 in the upper surface of the crossbar portion 115 of theproximal handle 116 that display a bi-stable (i.e., on-off states)indicator of a first color when overdrive is likely not a risk and asecond color when overdrive is likely a risk (e.g., curved cannulaassembly 210 has been fully deployed). In accordance with severalembodiments, there are advantageously two distinct states of operationand there is no transition zone between the two states. The overdriveindication mechanism may be configured to be activated only when a gearwheel 221 of the curved cannula assembly 210 is bottomed out (e.g.,fully engaged with the proximal handle 116 of the introducer cannula112). As shown in FIG. 3C, a lower (bottom) side surface of the proximalhandle 116 of the introducer cannula may include a cutout 124 adapted toreceive a portion of a flexible shaft of a treatment device (e.g.,radiofrequency probe comprised of nitinol or other flexible or shapememory material) and hold it in place and out of the way during atreatment procedure, thereby reducing stack height (e.g., byapproximately 3 inches (or approximately 75 mm) or more).

FIGS. 3D-3H illustrate various views and portions of embodiments ofintroducer stylets 114. FIG. 3D illustrates a side view of an introducerstylet 114. The introducer stylet 114 includes a proximal handle 126 anda distal elongate member or shaft 128. The proximal handle 126 comprisesan upper surface that is adapted for malleting by a mallet and a lowersurface that is adapted to facilitate removal of the introducer stylet114 by an operator. The length of the distal elongate member 128 mayrange from 8 mm to 14 mm (e.g., 8 mm, 8.5 mm, 9 mm, 9.5 mm, 10 mm, 10.5mm, 11 mm, 11.5 mm, 12 mm, 12.5 mm, 13 mm, 13.5 mm, 14 mm). The distalend portion 132 of the introducer stylet 114 may comprise a scallopedsection 133 (as shown more closely in FIG. 3E) to provide a releasemechanism for bone compaction. The scalloped section 133 may be designedto have a side profile shaped generally like an hourglass. The scallopedsection 133 may gradually taper from a full diameter proximal portion toa narrow-most middle portion and then gradually taper back to a fulldiameter distal portion. The taper may be symmetric or asymmetric. Thescalloped section 133 may comprise one scallop (or scooped-out region)or multiple scallops (or scooped-out regions) along the length of thedistal end portion 132. A distal tip 125 of the distal end portion 132may comprise a full diameter so as to be adapted to break apart bone(e.g., pedicle bone, cortical bone of a vertebral body). As the bone isbroken up by the distal tip 125 of the distal end portion 132, boneshards or chips can pack into a gap formed between the distal endportion 132 of the introducer stylet 114 and the inner surface of thedistal end portion of the introducer cannula 112, thereby making it moredifficult for the introducer stylet 114 to be removed from theintroducer cannula 112. In accordance with several embodiments, thescalloped section 133 of the introducer stylet 114 advantageouslyprovides the bone shards and fragments a place to fall into duringremoval of the introducer stylet 114 so as to facilitate easier removalof the introducer stylet 114.

FIGS. 3F-3H illustrate the introducer assembly 110 after the introducerstylet 114 has been inserted within the introducer cannula 112. Asindicated above, the proximal handle 116 of the introducer cannula 112may include mating or engagement features (e.g., coupling features 121)that facilitate automatic (e.g., snap-fit) engagement of the introducerstylet 114 with the proximal handle 116 of the introducer cannula 112.

The proximal handle 126 of the introducer stylet 114 includes analignment indicator 129, an anti-rotation tab 131, and a press button134. As shown best in FIG. 3G, the alignment indicator 129 is configuredto align with a corresponding alignment indicator 130 on the uppersurface of the crossbar portion 115 of the proximal handle 116 of theintroducer cannula 112 in order to ensure proper insertion and alignmentof the introducer stylet 114 with respect to the introducer cannula 112.The anti-rotation tab 131 is configured to be positioned within the slot117 of the proximal handle 116 of the introducer cannula 112 and toprevent rotation of the introducer stylet 114 with respect to theintroducer cannula 112 during malleting and orienting.

The press button 134 is integrally coupled to the anti-rotation tab 131such that pressing of the press button 134 extends the anti-rotation tab131 out of the constraint of the slot 117, thereby allowing theintroducer stylet 114 to rotate with respect to the introducer cannula112 (as shown in FIG. 3H). Pressing the press button 134 also releasesengagement of the introducer stylet 114 with the introducer cannula 112to enable removal of the introducer stylet 114 from the introducercannula 112. The proximal handle 126 of the introducer stylet 114 mayinclude internal ramps (not shown) configured to provide a mechanicaladvantage to assist in removal of the introducer stylet 114 from theintroducer cannula 112 (especially if bone shards have packed into gapsbetween the introducer stylet 114 and introducer cannula 112 makingremoval more difficult) as the proximal handle 126 is rotated (e.g.,120-degree rotation counter-clockwise). The combination of the scallopeddistal end portion design and the internal ramps in the proximal handle126 may provide increased reduction of removal forces by 50%-70%compared to a full diameter (e.g., no scalloped section) distal endportion design with no ramps in the proximal handle 126.

FIGS. 31 and 3J illustrate a side view and a top view of an embodimentof the curved cannula 212. The curved cannula 212 includes a proximalhandle 216, a threaded proximal shaft portion 220, a gear wheel 221, arigid support portion 223, and a distal polymeric shaft portion 224. Theproximal handle 216 includes a curved slot 217 and a curved ramp 231configured to facilitate insertion of the J-stylet 214 into and along acentral lumen of the curved cannula 212 extending from the proximalhandle 216 to an open distal tip 222 of the distal polymeric shaftportion 224. The central lumen of the curved cannula 212 may be coatedwith a medical grade silicone lubricant to improve tool insertion andremoval.

In the illustrated example, the gear wheel 221 comprises threadsconfigured to interface with corresponding threads of the threadedproximal shaft portion 220 such that rotation of the gear wheel 221causes controlled proximal and distal translation of the gear wheel 221along the threaded proximal shaft portion 220. The threaded proximalshaft portion 220 is sized such that when the gear wheel 221 is in itsdistal-most position, the distal tip 222 of the curved cannula 212 doesnot extend out of the open distal tip 122 of the introducer cannula 112when the curved cannula assembly 210 is fully inserted therein. The gearwheel 221 may spin freely about the threaded proximal shaft portion 220.The threads may comprise triple threads and the gear wheel 221 may beconfigured to traverse the entire length of the threaded proximal shaftportion 220 with four complete rotations of the gear wheel 221.

The rigid support portion 223 may comprise a biocompatible metal orother rigid material, such as stainless steel, titanium, platinum and/orthe like, so as to provide additional support to the curved cannula 212during insertion of the J-stylet 214. The distal polymeric shaft portion224 may be comprised of a thermoplastic, shape-memory polymer material(such as polyether ether ketone (PEEK), polyurethane, polyethyleneterephthalate (PET), and/or the like) and the distal end portion 225 ispre-curved (e.g., shape-set) to have a predetermined curve in a“resting” unconstrained configuration.

FIGS. 3K-3P illustrate an embodiment of the J-stylet 214. FIG. 3Killustrates a side view of the J-stylet 214 in a “resting” normal,unconstrained configuration or state and FIGS. 3L and 3M are close-upviews (side view and perspective view, respectively) of a curved distalend portion 227 of the J-stylet 214. The J-stylet 214 comprises aproximal handle 226 and a distal elongate shaft 218. The proximal handle226 comprises an upper surface that is adapted for malleting by a malletand a lower surface that is adapted to facilitate removal of theJ-stylet 214 by two or more (e.g., two, three, or four) fingers of anoperator. The upper surface of the proximal handle 216 includes analignment indicator 219 (shown, for example, in FIG. 3P) configured tobe aligned with the corresponding alignment indicator 130 of theintroducer cannula 112 to facilitate insertion, removal, and deploymentof the J-stylet 214 (and curved cannula assembly 210).

The distal elongate shaft 218 includes a curved distal end portion 227having an asymmetric curve profile along its length (e.g., the curveddistal end portion does not have a constant full diameter along itslength). A distal channeling tip 228 is sized and shaped to facilitatechanneling through cancellous bone along a curved path or trajectory.The curved distal end portion 227 comprises a springboard or platformsection 229 having a “D-shaped” cross-sectional profile, as shown, forexample, by the cross-section profile circle in FIG. 3M. The springboardor platform section 229 may be formed by mechanical grinding of atubular wire until the desired D-shaped cross section profile isachieved in which a top (e.g., upper) surface of the springboard orplatform section 229 is generally smooth and flat. The thickness (e.g.,vertical cross-sectional dimension) of the springboard or platformsection 229, the predefined set angulation or radius of curvature, andthe starting and ending points of the springboard or platform section229 along the length of the curved distal end portion 227 may be variedto provide J-stylets having different rigidity and bendingcharacteristics for different levels of vertebrae or different densitiesof bone.

In accordance with several embodiments, a thickness (e.g., a maximumvertical cross-sectional dimension from an upper surface of thespringboard or platform section 229 to a lower-most point on a lowersurface of the curved distal end portion) is between 40% and 85% (e.g.,between 40% and 60%, between 50% and 70%, between 50% and 75%, between60% and 70%, between 65% and 80%, between 70% and 85%, overlappingranges thereof, or any value within the recited ranges) of the thickness(e.g., diameter) of the adjacent regions of the curved distal endportion (e.g., the regions just proximal and just distal of the lengthof the springboard or platform section 229). Instead of percentages, thedifference in thickness dimensions could be represented as ratios (e.g.,between 2:5 and 4:5, between 2:5 and 3:5, between 1:2 and 3:4, between3:5 and 4:5, between 3:5 and 6:7). The ending point of the springboardor platform section 229 may be between 4.5 and 9 mm from a distalterminus of the distal elongate shaft 218. The starting point of thespringboard or platform section 229 may be between 230 mm and 245 mmfrom a proximal terminus of the distal elongate shaft 218.

According to several embodiments, the asymmetric curve profile (e.g.,profile with D-shaped cross-section) advantageously provides improvedcephalad-caudal steering because the curved distal end portion 227primarily bends inward and not laterally. In addition, the design andmaterial of the curved distal end portion 227 of the J-stylet 214 mayenable the angle of curvature of the curved distal end portion 227 toadvantageously remain relatively consistent and reproducible across avariety of bone densities, or regardless of bone environment. Forexample, in one embodiment, the design and material of the curved distalend portion 227 of the J-stylet 214 facilitates consistent andreproducible access to a posterior location (e.g., in posterior half ofthe vertebral body or to a location approximately 30%-50% of thedistance between the posterior-most aspect and the anterior-most aspectof the vertebral body along a sagittal axis or to a geometric center ormidpoint within the vertebral body for vertebral bodies having varyingbone densities or other desired target location in the vertebral body orother bone). In accordance with several embodiments, the curvature isdesigned to deviate by less than 25 degrees (e.g., less than 20 degrees,less than 15 degrees, less than 10 degrees) or less than 30% from thepredefined set curvature of the curved distal end portion 227 in anunconstrained configuration (even in hard bone).

The J-stylet 214 may be designed and adapted to exert a lateral force ofbetween 6 pounds and 8 pounds. The angle of curvature of the curveddistal end portion 227 (with respect to the central longitudinal axis ofthe straight proximal portion of the distal elongate shaft 218) of theJ-stylet 214 in the normal unconstrained state or configuration may bedesigned to be between 65 degrees and 80 degrees (e.g., 65 degrees, 70degrees, 75 degrees, 80 degrees, or any other value within the recitedrange). The radius of curvature of the curved distal end portion 227 mayrange from 11.5 mm to 15 mm (e.g., from 11.5 mm to 12 mm, from 12 mm to12.5 mm, from 12 mm to 13 mm, from 12.5 mm to 14 mm, from 13 mm to 15mm, overlapping ranges thereof, or any value within the recited ranges).The J-stylet 214 may be comprised of nitinol or other metallic alloymaterial.

FIGS. 3N and 30 are a perspective view and a side cross-section view,respectively, illustrating insertion of the curved distal end portion227 of the J-stylet 214 into the slot 217 of the proximal handle 216 ofthe curved cannula 212. As shown in FIG. 30, the slot 217 comprises acurved ramp 231 and a straight vertical backstop support 233 (e.g., withno trumpeted section) to facilitate insertion of the curved distal endportion 227 of the J-stylet 214. As indicated above, the curved cannula212 includes the rigid support portion 223 extending into and out of thethreaded shaft portion 220 to provide additional support upon insertionof the J-stylet 214 within the central lumen of the curved cannula 212.

FIGS. 3P and 3Q illustrate insertion of the curved cannula assembly 210into the introducer cannula 112. The curved distal end portion 225 ofthe curved cannula assembly 210 is inserted from a side angle (e.g., atabout a 65 to 75 degree angle (such as a 70 degree starting angle in oneembodiment) with respect to the central longitudinal axis LA of thedistal hypotube 118 of the introducer cannula 112) into the slot 117 andalong the ramp 141 in the proximal handle 116 and then down the centrallumen of the distal hypotube 118 of the introducer cannula 112 while thegear wheel 221 of the curved cannula 212 is in a distal-most positionalong the threaded proximal portion 220 of the curved cannula 212 so asto prevent inadvertent advancement of the curved distal portion of thecurved cannula assembly 210 beyond the open distal tip 122 of theintroducer cannula 112 until the operator is ready to do so.

FIG. 3Q is a close-up side cross-section view of the proximal portion ofthe introducer cannula 112 and the curved distal portion of the curvedcannula assembly 210 and illustrates insertion of the curved distal endportions of the assembled components of the curved cannula assembly 210into the introducer cannula 112. As shown, the introducer cannula 112 isshaped so as to provide a backstop support 143 generally aligned withthe inner surface of the central lumen of the hypotube 118 so as tofacilitate insertion and so that the curved distal end portion 225 ofthe distal polymeric shaft portion 224 of the curved cannula 212 doesnot pivot out of the introducer cannula 112 upon insertion. Inaccordance with several embodiments, the asymmetric “D-shaped”cross-sectional profile of the J-stylet 214 is advantageously designedto prevent twisting during insertion.

FIGS. 3R and 3S illustrate operation of the gear wheel 221 of the curvedcannula 212. As shown in FIG. 3R, the gear wheel 221 is rotated until itis in its distal-most position along the threaded proximal portion 220prior to insertion of the curved cannula assembly 210 within theintroducer cannula 112 so as to prevent inadvertent advancement of thecurved distal end portions 225, 227 of the curved cannula assembly 210out of the introducer cannula 112. As shown in FIG. 3S, the gear wheel221 is rotated to its proximal-most position along the threaded proximalportion 220 to enable full insertion of the curved cannula assembly 210within the introducer cannula 112 such that the curved distal endportions 225, 227 of the curved cannula assembly 210 extend out of theintroducer cannula 112 and along a curved path within the cancellousbone region of the vertebral body or other bone.

FIGS. 3T and 3U illustrate operation of a bail mechanism of the J-stylet214. The proximal handle 226 of the J-stylet 214 includes a bailactuator 250 configured to be toggled between a first “resting” or“inactive” configuration in which the bail actuator 250 is generallyaligned with (e.g., parallel or substantially parallel to) the uppersurface of the proximal handle 226 (as shown in FIG. 3T) and a second“active” configuration in which the bail actuator 250 is offset from theupper surface of the proximal handle 226 (as shown in FIG. 3U). The bailactuator 250 is configured to act as a lever to cause a slight axial(proximal-distal) movement of the J-stylet 214 with respect to thecurved cannula 212 as the bail actuator 250 is pivoted. When the bailactuator 250 is toggled to the “active” configuration, a flange 253 ofthe bail actuator 250 contacts the proximal handle 216 of the curvedcannula to cause proximal retraction of the J-stylet 214 with respect tothe curved cannula 212 such that the distal channeling tip 228 of theJ-stylet 214 resides completely within the curved cannula 212 and doesnot extend out of the open distal tip of the curved cannula 212. Inaccordance with several embodiments, the bail actuator 250 isadvantageously toggled to the “active” configuration (in which thedistal channeling tip 228 of the J-stylet 214 resides within the opendistal tip of the curved cannulas 212) upon insertion and removal of thecurved cannula assembly 210 from the introducer cannula 112 or theJ-stylet 214 from the curved cannula 212 (e.g., so as to avoid frictioncaused by interaction between two metal components). The upper surfaceof the bail actuator 250 may include an indicator 252 (e.g., coloredmarking or other visual indicator) that is visible to an operator whenthe bail actuator 250 is in the active configuration and hidden when thebail actuator 250 is in the inactive configuration.

FIG. 3V illustrates a side view of an embodiment of the straight stylet314 and FIG. 3W illustrates a distal portion of the straight stylet 314.The straight stylet 314 includes a proximal handle 316 and a distalelongate shaft 318. The proximal handle 316 includes an upper surfaceadapted for malleting by a mallet or application of pressure by a handor fingers of an operator. A radiopaque marker band 317 may bepositioned along the distal elongate shaft 318 at a positioncorresponding to the position when a distal channeling tip 319 of thestraight stylet 314 is exiting the open distal tip of the curved cannula212 as the straight stylet 314 is advanced through the curved cannula212. The length of the straight stylet 314 may be sized such that, whenthe straight stylet 314 is fully inserted within the curved cannula 212,the length of the portion of the straight stylet 314 extending beyondthe open distal tip of the curved cannula 212 is between 25 and 50 mm(e.g., between 25 mm and 35 mm, between 30 mm and 40 mm, between 35 mmand 45 mm, between 40 and 50 mm, overlapping ranges thereof, or anyvalue within the recited ranges). The diameter of the straight stylet314 is sized so as to be inserted within and through the central lumenof the curved cannula 212.

The distal elongate shaft 318 comprises an inner flexible, shape memorycore 360 extending from the proximal handle 316 to the distal channelingtip 319 of the straight stylet 314 and a polymeric outer layer 365extending from the proximal handle 316 to a distal end of the distalelongate shaft 318 but stopping short (or proximal to) the distalchanneling tip 319 so that the inner core 360 protrudes out of the outerlayer 365. The straight stylet 314 is flexible enough to bend totraverse the curved distal end portion 225 of the curved cannula 212without significant friction but sufficiently rigid so as to maintain astraight path once the straight stylet 314 exits the open distal tip ofthe curved cannula 212. The inner core 360 of the straight stylet 314may comprise nitinol or other metallic alloy or other flexible material.The outer layer 365 may be comprised of a more rigid, polymeric material(such as PEEK, polyurethane, PET, and/or the like).

FIGS. 3X-3Z illustrate an embodiment of an introducer drill 440 and itsinteraction with the introducer cannula 112. A kit or system of accessinstruments (e.g., a kit or kit module designed for accessing hard, orhigh-density, bone) may optionally include the introducer drill 440.FIG. 3X is a side view of an embodiment of the introducer drill 440. Theintroducer drill 440 includes a proximal handle 446 and an elongatedrill shaft 447. The proximal handle 446 may comprise a generallyT-shaped design and may comprise a soft-grip overmolding. The length ofthe elongate drill shaft 447 may be sized so as to extend from 20 mm to35 mm beyond the open distal tip of the introducer cannula 112 when theintroducer drill 440 is fully inserted within the introducer cannula112. The elongate drill shaft 447 may include a solid proximal portion448 and a fluted distal portion 449.

FIG. 3Y is a close-up perspective view of the fluted distal portion 449.The fluted distal portion 449 may comprise a distal cutting tip 450having a 90 degree cutting angle. The drill flutes 452 of the fluteddistal portion 449 may be adapted to taper away from the distal cuttingtip 450 (which is a reverse taper or opposite the direction of taper ofa typical drill bit) so as to facilitate improved bone chip packingwithin the open flute volume as bone chips and fragments are generatedby operation of the introducer drill 440. The distal cutting tip 450 mayhave a point angle of between 65 and 75 degrees and a chisel edge angleof between 115 and 125 degrees. The flutes may advantageously be deeperand wider than typical drill bits because the elongate drill shaft 447is supported by a rigid introducer cannula 112 surrounding at least aportion of the length of the elongate drill shaft (and a portion of thelength of the fluted distal portion in most instances) during use. Thedrill flutes 452 may have a helix angle of between 12 degrees and 18degrees (e.g., between 12 degrees and 14 degrees, between 13 degrees and17 degrees, between 14 degrees and 16 degrees, between 14 degrees and 18degrees, overlapping ranges thereof, or any value within the recitedranges). The fluted distal portion 449 may include two flutes having alength of between 70 mm and 85 mm.

The open flute volume of the fluted distal portion 449 may beadvantageously configured to hold all or substantially all (e.g., morethan 75%, more than 80%, more than 85%, more than 90%) of thesignificantly-sized bone chips or fragments removed by the introducerdrill 440 as the introducer drill 440 is removed from the introducercannula 112, thereby reducing the bone fragments left behind in the bone(e.g., vertebral body) or in the introducer cannula 112. In someembodiments, the open flute volume of the fluted distal portion 449 isadapted to hold about 2 ccs of bone. The fluted distal portion 449 mayexhibit web tapering (e.g., increase in width or depth, or angle withrespect to longitudinal axis of the flutes) along its length from distalto proximal (e.g., reverse taper). There may be no web taper forapproximately the first 25 mm at the distal-most region. The web tapermay then increase gradually until a maximum web taper is reached nearthe proximal end of the fluted distal portion 449 so as to facilitatepushing of the bone fragments or chip upward (or proximally) along thefluted distal portion 449. For example, the fluted distal portion 449may have a negative draft (e.g., 0.77″ or ˜20 mm negative draft).

FIG. 3Z illustrates the introducer drill 440 fully inserted and engagedwith the proximal handle 116 of the introducer cannula 112. Theintroducer drill 440 is sized so as to be inserted within the centralopening 120 of the proximal handle 116 of the introducer cannula 112 andadvanced through the central lumen of the hypotube 118 of the introducercannula 112. The proximal handle 446 of the introducer drill 440 isconfigured to engage with the coupling or mating features 121 of theproximal handle 116.

FIGS. 3AA-3HH illustrate an embodiment of steps of a method of using theaccess tools to facilitate access to a location within a vertebral body500 for treatment (e.g., modulation of intraosseous nerves, such as abasivertebral nerve, bone cement delivery for treatment of vertebralfractures, and/or ablation of bone tumors). With reference to FIG. 3AA,the distal portion of the introducer assembly 110 (including the distaltip 125 of the introducer stylet 114 and the distal tip of theintroducer cannula 112) are inserted through a pedicle 502 adjacent thevertebral body 500 by malleting on the proximal handle of the introducerstylet 114 after insertion and aligned engagement of the introducerstylet 114 within the introducer cannula 112.

In accordance with several embodiments, the method may optionallyinclude removing the introducer stylet after initial penetration intothe pedicle 502 (for example, if the operator can tell that the densityof the bone is going to be sufficiently dense or hard that additionalsteps and/or tools will be needed to obtain a desired curved trajectoryto access a posterior portion (e.g., posterior half) of the vertebralbody 500. With reference to FIG. 3BB, the method may optionally includeinserting the introducer drill 440 into and through the introducercannula 112 to complete the traversal of the pedicle 502 and penetrationthrough a cortical bone 503 region of the vertebral body 500 until acancellous bone region 504 of the vertebral body 500 is reached. Theintroducer drill 550 may be advanced into the cancellous bone region 504(especially if the cancellous bone region 504 is determined to besufficiently hard or dense) or the advancement may stop at the borderbetween the cortical bone region 503 and the cancellous bone region 504.This step may involve both rotating the introducer drill 440 andmalleting on the proximal handle 446 of the introducer drill 440 orsimply rotating the introducer drill 440 without malleting on theproximal handle 446. With reference to FIG. 3CC, the introducer drill440 may be removed and the introducer stylet 114 may be re-insertedwithin the introducer cannula 112. With reference to FIG. 3DD, theintroducer assembly 110 may then be malleted so as to advance the distaltip 122 of the introducer cannula 112 to the entry site into (or within)the cancellous bone region 504 of the vertebral body 500. The introducerstylet 114 may then be removed from the introducer cannula 112.

The curved cannula assembly 210 may then be inserted within theintroducer cannula 112 with the gear wheel 221 in the distal-mostposition so as to prevent inadvertent advancement of the curved cannulaassembly 210 out of the open distal tip 122 of the introducer cannula112 prematurely. With reference to FIG. 3EE, after rotation of the gearwheel 221 to a more proximal position, the curved cannula assembly 210can be malleted so as to advance the collective curved distal endportions of the curved cannula assembly 210 together out of the distaltip 122 of the introducer cannula 112 and along a curved path within thecancellous bone region 504. With reference to FIG. 3FF, the J-stylet 214may then be removed from the curved cannula 212, with the curved cannula212 remaining in position. In accordance with several embodiments, thepath formed by the prior instruments may advantageously allow the curvedcannula assembly 210 to have a head start and begin curving immediatelyupon exiting the open distal tip 122 of the introducer cannula 112.

With reference to FIG. 3GG, if a further straight path beyond the curvedpath is desired to reach a target treatment location, the straightstylet 314 may be inserted through the curved cannula 212 such that thedistal channeling tip 319 of the straight stylet extends beyond the opendistal tip of the curved cannula 212 and along a straight path towardthe target treatment location (e.g., a basivertebral nerve trunk orbasivertebral foramen). In some embodiments, the straight stylet 314 maynot be needed and this step may be skipped.

With reference to FIG. 3HH, a treatment device 501 (e.g., a flexiblebipolar radiofrequency probe) may be inserted through the curved cannula212 (after removal of the straight stylet 314 if used) and advanced outof the open distal tip of the curved cannula 212 to the target treatmentlocation. The treatment device 501 may then perform the desiredtreatment. For example, if the treatment device 501 is a radiofrequencyprobe, the treatment device 501 may be activated to ablate intraosseousnerves (e.g., a basivertebral nerve) or a tumor within the vertebralbody 500. Bone cement or other agent, or a diagnostic device (such as anerve stimulation device or an imaging device to confirm ablation of anerve) may optionally be delivered through the curved cannula 212 afterthe treatment device 501 is removed from the curved cannula 212.

At certain levels of the spine (e.g., sacral and lumbar levels) and forcertain patient spinal anatomies that require a steeper curve to accessa desired target treatment location within the vertebral body, acombination curette/curved introducer may first be inserted to start acurved trajectory (e.g., create an initial curve or shelf) into thevertebra. The curette may have a pre-curved distal end portion or beconfigured such that the distal end portion can be controllablyarticulated or curved (e.g., manually by a pull wire or rotation of ahandle member coupled to one or more pull wires coupled to the distalend portion or automatically by a robotic or artificial intelligencedriven navigation system). The combination curette/curved introducer maythen be removed and the outer straight cannula and inner curvedcannula/curved stylet assembly may then be inserted to continue thecurve toward the target treatment location.

In accordance with several implementations, any of the access tools(e.g., cannula or stylet) or treatment devices may comprise arheological and/or magnetizable material (e.g., magnetorheologicalfluid) along a distal end portion of the access tool that is configuredto be curved in situ after insertion to a desired location within bone(e.g., vertebra). A magnetic field may be applied to the distal endportion of the access tool and/or treatment device with the magnetizablefluid or other material and adjusted or varied using one or morepermanent magnets or electromagnets to cause the distal end portion ofthe access tool and/or treatment device to curve toward the magneticfield. In some implementations, a treatment probe may include a magneticwire along a portion of its length (e.g., a distal end portion). Voltageapplied to the magnetic wire may be increased or decreased to increaseor decrease a curve of the magnetic wire. These implementations mayadvantageously facilitate controlled steering without manual pull wiresor other mechanical mechanisms. The voltage may be applied byinstruments controlled and manipulated by an automated robotic controlsystem, such as the robotic system described in connection with FIG. 7.

The treatment devices (e.g., treatment probes) may be any device capableof modulating tissue (e.g., nerves, tumors, bone tissue). Any energydelivery device capable of delivering energy can be used (e.g., RFenergy delivery devices, microwave energy delivery devices, laserdevices, infrared energy devices, other electromagnetic energy deliverydevices, ultrasound energy delivery devices, and the like). Thetreatment device 501 may be an RF energy delivery device. The RF energydelivery device may include a bipolar pair of electrodes at a distal endportion of the device. The bipolar pair of electrodes may include anactive tip electrode and a return ring electrode spaced apart from theactive tip electrode. The RF energy delivery device may include one ormore temperature sensors (e.g., thermocouples, thermistors) positionedon an external surface of, or embedded within, a shaft of the energydelivery device. The RF energy delivery device may not employ internallycirculating cooling, in accordance with several implementations.

In some implementations, water jet cutting devices may be used tomodulate (e.g., denervate) nerves. For example, a water jet cutter maybe configured to generate a very fine cutting stream formed by a veryhigh-pressure jet of water. For example, the pressure may be in therange of 15 MPa to 500 MPa (e.g., 15 MPa to 50 MPa, 30 MPa-60 MPa, 50MPa-100 MPa, 60 MPa-120 MPa, 100 MPa-200 MPa, 150 MPa-300 MPa, 300MPa-500 MPa, overlapping ranges thereof, or any value within the recitedranges). In some implementations, a chemical neuromodulation toolinjected into a vertebral body or at an endplate may be used to ablateor otherwise modulate nerves or other tissue. For example, the chemicalneuromodulation tool may be configured to selectively bind to a nerve orendplate. In some implementations, a local anesthetic (e.g., liposomallocal anesthetic) may be used inside or outside a vertebral body orother bone to denervate or block nerves. In some implementations,brachytherapy may be used to place radioactive material or implantswithin the vertebral body to deliver radiation therapy sufficient toablate or otherwise denervate the vertebral body. In someimplementations, chymopapain injections and/or condoliase injections maybe used (e.g., under local anesthesia). Phototherapy may be used toablate or otherwise modulate nerves after a chemical or targeting agentis bound to specific nerves or to a vertebral endplate.

In accordance with several implementations, thermal energy may beapplied within a cancellous bone portion (e.g., by one or moreradiofrequency (RF) energy delivery instruments coupled to one or moreRF generators) of a vertebral body. The thermal energy may be conductedby heat transfer to the surrounding cancellous bone, thereby heating upthe cancellous bone portion. In accordance with several implementations,the thermal energy is applied within a specific frequency range andhaving a sufficient temperature and over a sufficient duration of timeto heat the cancellous bone such that the basivertebral nerve extendingthrough the cancellous bone of the vertebral body is modulated. Inseveral implementations, modulation comprises permanent ablation ordenervation or cellular poration (e.g., electroporation). In someimplementations, modulation comprises temporary denervation orinhibition. In some implementations, modulation comprises stimulation ordenervation without necrosis of tissue.

For thermal energy, temperatures of the thermal energy may range fromabout 70 to about 115 degrees Celsius (e.g., from about 70 to about 90degrees Celsius, from about 75 to about 90 degrees Celsius, from about83 to about 87 degrees Celsius, from about 80 to about 100 degreesCelsius, from about 85 to about 95 degrees Celsius, from about 90 toabout 110 degrees Celsius, from about 95 to about 115 degrees Celsius,or overlapping ranges thereof). The temperature ramp may range from0.1-5 degrees Celsius/second (e.g., 0.1-1.0 degrees Celsius/second, 0.25to 2.5 degrees Celsius/second, 0.5-2.0 degrees Celsius/second, 1.0-3.0degrees Celsius/second, 1.5-4.0 degree Celsius/second, 2.0-5.0 degreesCelsius/second). The time of treatment may range from about 10 secondsto about 1 hour (e.g., from 10 seconds to 1 minute, 1 minute to 5minutes, from 5 minutes to 10 minutes, from 5 minutes to 20 minutes,from 8 minutes to 15 minutes, from 10 minutes to 20 minutes, from 15minutes to 30 minutes, from 20 minutes to 40 minutes, from 30 minutes to1 hour, from 45 minutes to 1 hour, or overlapping ranges thereof).Pulsed energy may be delivered as an alternative to or in sequence withcontinuous energy. For radiofrequency energy, the energy applied mayrange from 350 kHz to 650 kHz (e.g., from 400 kHz to 600 kHz, from 350kHz to 500 kHz, from 450 kHz to 550 kHz, from 500 kHz to 650 kHz,overlapping ranges thereof, or any value within the recited ranges, suchas 450 kHz±5 kHz, 475 kHz±5 kHz, 487 kHz±5 kHz). A power of theradiofrequency energy may range from 5 W to 30 W (e.g., from 5 W to 15W, from 5 W to 20 W, from 8 W to 12 W, from 10 W to 25 W, from 15 W to25 W, from 20 W to 30 W, from 8 W to 24 W, and overlapping rangesthereof, or any value within the recited ranges). In accordance withseveral implementations, a thermal treatment dose (e.g., using acumulative equivalent minutes (CEM) 43 degrees Celsius thermal dosecalculation metric model) is between 200 and 300 CEM (e.g., between 200and 240 CEM, between 230 CEM and 260 CEM, between 240 CEM and 280 CEM,between 235 CEM and 245 CEM, between 260 CEM and 300 CEM) or greaterthan a predetermined threshold (e.g., greater than 240 CEM). The CEMnumber may represent an average thermal cumulative dose value at atarget treatment region or location and may represent a number thatexpresses a desired dose for a specific biological end point. Thermaldamage may occur through necrosis or apoptosis.

Cooling may optionally be provided to prevent surrounding tissues frombeing heated during the nerve modulation procedure. The cooling fluidmay be internally circulated through the delivery device from and to afluid reservoir in a closed circuit manner (e.g., using an inflow lumenand an outflow lumen). The cooling fluid may comprise pure water or asaline solution having a temperature sufficient to cool electrodes(e.g., 2-10 degrees Celsius, 5-10 degrees Celsius, 5-15 degreesCelsius). Cooling may be provided by the same instrument used to deliverthermal energy (e.g., heat) or a separate instrument. In accordance withseveral implementations, cooling is not used.

In some implementations, ablative cooling may be applied to the nervesor bone tissue instead of heat (e.g., for cryoneurolysis or cryoablationapplications). The temperature and duration of the cooling may besufficient to modulate intraosseous nerves (e.g., ablation, or localizedfreezing, due to excessive cooling). The cold temperatures may destroythe myelin coating or sheath surrounding the nerves. The coldtemperatures may also advantageously reduce the sensation of pain. Thecooling may be delivered using a hollow needle under fluoroscopy orother imaging modality.

In some implementations, one or more fluids or agents may be deliveredto a target treatment site to modulate a nerve. The agents may comprisebone morphogenetic proteins, for example. In some implementations, thefluids or agents may comprise chemicals for modulating nerves (e.g.,chemoablative agents, alcohols, phenols, nerve-inhibiting agents, ornerve stimulating agents). The fluids or agents may be delivered using ahollow needle or injection device under fluoroscopy or other imagingmodality.

One or more treatment devices (e.g., probes) may be used simultaneouslyor sequentially. For example, the distal end portions of two treatmentdevices may be inserted to different locations within a vertebral bodyor other bone or within different vertebral bodies or bones.Radiofrequency treatment probes may include multiple electrodesconfigured to act as monopolar, or unipolar, electrodes or as pairs ofbipolar electrodes. The treatment device(s) may also be pre-curved orcurveable such that the curved stylet is not needed or may have sharpdistal tips such that additional sharpened stylets are not needed. Insome implementations, any or all of the access tools and the treatmentdevices are MR-compatible so as to be visualized under MR imaging.

The one or more treatment devices (e.g., probes such as radiofrequencyprobes, treatment device 501 of a kit or system) may include anindicator configured to alert a clinician as to a current operationstate of the treatment device. For example, the indicator may include alight ring disposed along a length of, and extending around acircumference of, the treatment device. The light ring may be configuredto light up with different colors and/or exhibit other visible effects(e.g., pulsing on and off with certain patterns). The one or moretreatment devices may also be configured to provide audible alerts(e.g., beeps having a certain frequency or intonation) corresponding todifferent operational states. In one implementation, the light ring maybe dark or not lit up when the treatment device is not connected to aradiofrequency generator or not ready for RF energy delivery. The lightring may pulse at a first rate (e.g., 1 pulse every 2-3 seconds) toindicate an operational state in which the treatment device andgenerator system are ready to initiate RF energy delivery. The lightring may be continuously lit up to indicate an operational state inwhich the treatment device is actively delivering RF energy. The lightring may pulse at a second rate different than (e.g., faster than,slower than) the first rate to indicate an operational state in which anerror has been detected by the generator or if a particular treatmentparameter is determined to be outside an acceptable range of values. Inone implementation, the second rate is greater than the first rate(e.g., 2 pulses per second). Haptic feedback may also be provided to theclinician for at least some of the operational states to provide afurther alert in addition to a visible alert.

In some implementations, the treatment device (e.g., treatment device501) includes a microchip that is pre-programmed with treatmentparameters (e.g., duration of treatment, target temperature, temperatureramp rate). Upon electrical connection of the treatment device to thegenerator, the treatment parameters are transmitted to the generator anddisplayed on a display of the generator to provide confirmation ofdesired treatment to a clinician.

FIG. 4 illustrates a front view of an embodiment of a generator 400(e.g., radiofrequency energy generator). The generator 400 includes aninstrument connection port 405 to which a treatment device (e.g., RFenergy delivery probe) may be connected. The generator 400 may beconfigured for use without a neutral electrode (e.g., grounding pad).The instrument connection port 605 is surrounded by an indicator light406 configured to illuminate when the treatment device is properlyconnected to the instrument connection port 405. As shown, the indicatorlight 406 may comprise a circular LED indicator light. The indicatorlight 406 may be configured to continuously illuminate in a solid color(e.g., white, blue, green) when a treatment device is connected to theinstrument connection port 405. The indicator light 406 may flash at afirst pulsing rate (e.g., 1 Hz) to prompt a clinician to connect thetreatment device to the instrument connection port 405. The indicatorlight 406 may flash at a second pulsing rate different than (e.g.,faster than) the first pulsing rate (e.g., 2 Hz, 3 Hz, 4 Hz) to indicatean error condition.

The generator 400 also includes a display 408 configured to displayinformation to the clinician or operator. During startup and use, thecurrent status of the generator 400 and energy delivery (treatment)parameters may be displayed on the display 408. During energy delivery,the display 408 may be configured to display remaining treatment time,temperature, impedance, and power information (alphanumerically and/orgraphically). For example, graphical representations of power vs. timeand impedance vs. time may be displayed. In one implementation, thedisplay may comprise a color, active matrix display. The generator 400further includes a start/pause button 410 configured to be pressed by anoperator to initiate and stop energy delivery. Similar to the indicatorlight 406 surrounding the instrument connection port 405, a secondindicator light 412 may surround the start/pause button 410. The secondindicator light 412 may also comprise a circular LED indicator light.The second indicator light 412 may be configured to continuouslyilluminate in a solid color (e.g., white, blue, green) when thegenerator 400 is powered on and ready to initiate energy delivery. Theindicator light 412 may flash at a first pulsing rate (e.g., 1 Hz) toprompt a clinician to press the start/pause button 410 to initiateenergy delivery. The indicator light 412 may flash at a second pulsingrate different than (e.g., faster than) the first pulsing rate (e.g., 2Hz, 3 Hz, 4 Hz) when energy delivery has been paused or stopped. Thegenerator 400 may also be configured to output audible alerts indicativeof the different operating conditions (e.g., to coincide with the outputof the indicator lights 406, 412.

The generator 400 may also include a power button 414 configured topower on and off the generator 400, a standby power indicator light 416configured to illuminate (e.g., in solid green color) when an AC powerswitch (not shown) of the generator 400 is switched on, an RF activeindicator light 417 configured to illuminate (e.g., in solid blue color)during RF energy delivery, and a system fault indicator light 418configured to illuminate (e.g., in solid red color) during a systemfault condition. The generator 400 may also include user input buttons420 configured to facilitate navigation and selection of options (e.g.,menu options, configuration options, acknowledgement requests) thatappear on the display 408 (e.g., arrow buttons to toggle up and downbetween options and an “enter” button for user selection of a desiredoption).

Access to Locations Outside Vertebral Body

For access to locations outside bone (e.g., extraosseous locations, suchas outside a vertebral body), visualization or imaging modalities andtechniques may be used to facilitate targeting. For example, a foramenof a vertebral body (e.g., basivertebral foramen) may be located usingMRI guidance provided by an external MR imaging system, CT guidanceprovided by an external tomography imaging system, fluoroscopic guidanceusing an external X-ray imaging system, and/or an endoscope insertedlaparoscopically. Once the foramen is located, therapy (e.g., heat orenergy delivery, chemoablative agent delivery, cryotherapy,brachytherapy, and/or mechanical severing) may be applied to the foramensufficient to modulate (e.g., ablate, denervate, stimulate) any nervesentering through the foramen. For example, an endoscope may be used tolocate the foramen under direct visualization and then the basivertebralnerve may be mechanically transected near the foramen. In someimplementations, an intervertebral disc and vertebral body may bedenervated by treating (e.g., ablating) a sinuvertebral nerve prior tothe sinuvertebral nerve branching into the basivertebral nerve thatenters the basivertebral foramen of the vertebral body. Becausevertebral endplates are cartilaginous, radiation or high-intensityfocused ultrasound energy may be applied to vertebral endplates from alocation external to a subject's body altogether to denervate nerves inthe vertebral endplates.

Target Identification and Patient Screening

In accordance with several implementations, target, or candidate,vertebrae for treatment can be identified prior to treatment. Thetarget, or candidate, vertebrae may be identified based onidentification of various types of, or factors associated with, endplatedegeneration and/or defects (e.g., focal defects, erosive defects, rimdefects, corner defects, all of which may be considered pre-Modic changecharacteristics). For example, one or more imaging modalities (e.g.,MRI, CT, X-ray, fluoroscopic imaging) may be used to determine whether avertebral body or vertebral endplate exhibits active Modiccharacteristics or “pre-Modic change” characteristics (e.g.,characteristics likely to result in Modic changes, such as Type 1 Modicchanges that include findings of inflammation and edema or type 2 Modicchanges that include changes in bone marrow (e.g., fibrosis) andincreased visceral fat content). For example, images obtained via MRI(e.g., IDEAL MRI) may be used to identify (e.g., via application of oneor more filters) initial indications or precursors of edema orinflammation at a vertebral endplate prior to a formal characterizationor diagnosis as a Type 1 Modic change. Examples of pre-Modic changecharacteristics could include mechanical characteristics (e.g., loss ofsoft nuclear material in an adjacent intervertebral disc of thevertebral body, reduced disc height, reduced hydrostatic pressure,microfractures, focal endplate defects, erosive endplate defects, rimendplate defects, corner endplate defects, osteitis, spondylodiscitis,Schmorl's nodes) or bacterial characteristics (e.g., detection ofbacteria that have entered an intervertebral disc adjacent to avertebral body, a disc herniation or annulus tear which may have allowedbacteria to enter the intervertebral disc, inflammation or newcapilarisation that may be caused by bacteria) or other pathogeneticmechanisms that provide initial indications or precursors of potentialModic changes or vertebral endplate degeneration or defects.

Accordingly, vertebral bodies may be identified as target candidates fortreatment before Modic changes occur (or before painful symptomsmanifest themselves to the patient) so that the patients can beproactively treated to prevent, or reduce the likelihood of, chronic lowback pain before it occurs. In this manner, the patients will not haveto suffer from debilitating lower back pain for a period of time priorto treatment. Modic changes may or may not be correlated with endplatedefects and may or may not be used in candidate selection or screening.In accordance with several embodiments, Modic changes are not evaluatedand only vertebral endplate degeneration and/or defects (e.g., pre-Modicchange characteristics prior to onset or prior to the ability toidentify Modic changes) are identified. Rostral and/or caudal endplatesmay be evaluated for pre-Modic changes (e.g., endplate defects thatmanifest before Modic changes that may affect subchondral and vertebralbone marrow adjacent to a vertebral body endplate).

In some implementations, a level of biomarker(s) (e.g., substance P,cytokines, high-sensitivity C-reactive protein, or other compoundsassociated with inflammatory processes and/or pain and/or that correlatewith pathophysiological processes associated with vertebral endplatedegeneration or defects (e.g., pre-Modic changes) or Modic changes suchas disc resorption, Type III and Type IV collagen degradation andformation, or bone marrow fibrosis) may be obtained from a patient(e.g., through a blood draw (e.g., blood serum) or through a sample ofcerebrospinal fluid) to determine whether the patient is a candidate forbasivertebral nerve ablation treatment (e.g., whether they have one ormore candidate vertebral bodies exhibiting factors or symptomsassociated with endplate degeneration or defects (e.g., pre-Modic changecharacteristics)). Cytokine biomarker samples (e.g., pro-angiogenicserum cytokines such as vascular endothelial growth factor (VEGF)-C,VEGF-D, tyrosine-protein kinase receptor 2, VEGF receptor 1,intercellular adhesion molecule 1, vascular cell adhesion molecule 1)may be obtained from multiple different discs or vertebral bodies orforamina of the patient and compared with each other in order todetermine the vertebral bodies to target for treatment. Other biomarkersmay be assessed as well, such as neo-epitopes of type III and type IVpro-collagen (e.g., PRO-C3, PRO-C4) and type III and type IV collagendegradation neo-epitopes (e.g., C3M, C4M).

In some implementations, samples are obtained over a period of time andcompared to determine changes in levels over time. For example,biomarkers may be measured weekly, bi-monthly, monthly, every 3 months,or every 6 months for a period of time and compared to analyze trends orchanges over time. If significant changes are noted between thebiomarker levels (e.g., changes indicative of endplate degeneration ordefects (e.g., pre-Modic change characteristics) or Modic changes, asdescribed above), treatment may be recommended and performed to preventor treat back pain. Biomarker levels (e.g., substance P, cytokineprotein levels, PRO-C3, PRO-C4, C3M, C4M levels) may be measured usingvarious in vivo or in vitro kits, systems, and techniques (e.g.,radio-immunoassay kits/methods, enzyme-linked immunosorbent assay kits,immunohistochemistry techniques, array-based systems, bioassay kits, invivo injection of an anticytokine immunoglobulin, multiplexedfluorescent microsphere immune-assays, homogeneous time-resolvedfluorescence assays, bead-based techniques, interferometers, flowcytometry, etc.). Cytokine proteins may be measured directly orindirectly, such as by measuring mRNA transcripts.

The identification of pre-Modic change characteristics may involvedetermining a quantitative or qualitative endplate score based onseverity, extent, and/or quantity of the identified pre-Modic changecharacteristics (e.g., vertebral endplate defects) and vertebrae havinga quantitative endplate score above a threshold may be deemed aspotential candidates for treatment (e.g., basivertebral nerve ablation).The pre-Modic change characteristics may be combined with age, gender,body mass index, bone mineral density measurements, back pain history,and/or other known risk factors for vertebral endplate degeneration ordefects (such as smoking, occupational or recreational physical demandsor situations) in identifying candidate patients and/or candidatevertebral bodies for treatment (e.g., basivertebral nerve ablation).

Lesion Shaping and Formation

Shaping

In some implementations, a target treatment region within a vertebralbody may be clarified using pre-operative imaging (e.g., using bilateralfluoroscopy images or both anterior-posterior and lateral fluoroscopyimages) of the vertebral body. The target treatment region may beidentified as where a tip of a channeling stylet transects abasivertebral foramen (based on the images). In some implementations, anideal target treatment region may be located at or about 1 cm from aposterior wall of the vertebral body (e.g., between 10 mm and 11 mm,between 10.5 mm and 11.5 mm, 10 mm, 10.5 mm, 11 mm, 11.5 mm). Forcertain vertebral body levels, it may be desirable to target an edge ofa safety boundary.

In accordance with several implementations, lesion zones, or ablationzones, may advantageously be preferentially shaped to provide sufficientcoverage to ablate a basivertebral nerve or other intraosseous nerve butnot permanently ablate or damage surrounding or adjacent tissue, therebyminimizing extent of injury or damage. The shape of the lesion zone maybe preferentially shaped by providing specific energy treatmentalgorithms or recipes. For example, a certain amount of power may beapplied to heat a target treatment zone to within a certain temperaturerange for a period of time within a certain time range sufficient toform a lesion zone that ablates a targeted nerve within bone (e.g.,basivertebral nerve) but limits the size of the lesion zone to isolatethe nerve (e.g., a focused or targeted lesion zone).

In implementations involving radiofrequency energy delivery devices,multiple different sized electrodes may be included along the deviceand/or the layout of the electrodes may be varied to increase a diameterand/or length (e.g., major diameter along a long axis of the zone and/orminor diameter along a short axis of the zone) or otherwise adjust ashape of a lesion zone. The frequency applied to the electrodes, thepower applied to the electrodes, the target temperature, cooling of theelectrodes, duration of treatment, and/or the length or diameter of theelectrodes may be varied to vary an overall diameter or shape of alesion. Pulsing of the applied power may also be used to change lesionshape. Power output may be adjusted based on real-time temperaturemeasurements obtained from one or more temperature sensors positionedwithin and/or along the treatment device or in separate temperatureprobes inserted within the target treatment zone. The treatment devicemay also be moved (e.g., rotated and/or translated) at various timesduring the treatment procedure to affect lesion shape. In other words,the lesion shape may be controlled by rotational attributes. In someimplementations, shaping of lesions is effected by controlling an amountof electrode surface area that is exposed (e.g., masking of electrodesto control delivery of energy). In accordance with severalimplementations, a thermal treatment dose (e.g., using a cumulativeequivalent minutes (CEM) 43 degrees Celsius model) is between 200 and300 CEM (e.g., between 200 and 240 CEM, between 230 CEM and 260 CEM,between 235 CEM and 245 CEM, between 240 CEM and 280 CEM, between 260CEM and 300 CEM) or greater than a predetermined threshold (e.g.,greater than 240 CEM).

In some implementations, a heating, or lesion, zone is established andcontrolled within a vertebral body so as not to heat any portion of thevertebral body within 1 cm of the posterior wall (e.g., posterior-mostborder) of the vertebral body. In some implementations, the targetedheating zone is maintained to a region that is between about 10% andabout 80%, between about 5% and about 70%, between about 10% and about65%, between about 20% and about 60%, between about 30% and about 55%,or overlapping ranges thereof, of the distance from the posterior wallto the anterior wall of the vertebral body. The heating zone may bespecifically designed and configured to encompass a terminus of abasivertebral nerve or other intraosseous nerve (or of a basivertebralforamen). The terminus may be located approximately mid-body in thevertebral body (e.g., approximately 30%-50% across the sagittalvertebral body width). In various implementations, the heating zone mayrange from 8 mm to 20 mm (e.g., 8 to 10 mm, 10 to 12 mm, 11 to 13 mm, 12to 14 mm, 13 to 15 mm, 14 to 20 mm, overlapping ranges thereof, or anyvalue within the recited ranges) in maximum dimension (e.g., largestdiameter).

In accordance with several embodiments, a desired target treatmentlocation or region of a vertebral body may be any location at which 75%of the basivertebral nerve branches are sufficiently denervated (e.g.,ablated) by applying a thermal treatment dose (e.g., using a cumulativeequivalent minutes (CEM) 43 degrees Celsius model) of between 200 and300 CEM (e.g., between 200 and 240 CEM, between 230 CEM and 260 CEM,between 235 CEM and 245 CEM, between 240 CEM and 280 CEM, between 260CEM and 300 CEM) or greater than a predetermined threshold (e.g.,greater than 240 CEM). In some embodiments, the desired target treatmentlocation or region of a vertebral body is a location that is no moreanterior than a location corresponding to 25% arborization of nervebranches of the basivertebral nerve from the exit point at thebasivertebral foramen. Arborization may be defined by its ordinarymeaning in a medical dictionary and may mean branching off of nervebranches from a main origin nerve (e.g., terminus or entry/exit point ofa basivertebral nerve in a vertebral body). 25% arborization may meanthat 25% of the total nerve branches within a particular vertebral bodyhave branched off from a main origin nerve. In some embodiments, thedesired target treatment location comprises a geometric center ormidpoint of the vertebral body. The treatment (e.g., basivertebral nerveablation) may be performed within multiple different vertebral bodiessimultaneously or sequentially using the same parameters. The vertebralbodies may be adjacent or spaced-apart vertebral bodies of the samespine level or a different spine level (e.g., sacral, lumbar, thoracic,cervical).

In accordance with several embodiments, a thermal treatment dose (e.g.,using a cumulative equivalent minutes (CEM) 43 degrees Celsius model) ofbetween 200 and 300 CEM (e.g., between 200 and 240 CEM, between 230 CEMand 260 CEM, between 235 CEM and 245 CEM, between 240 CEM and 280 CEM,between 260 CEM and 300 CEM) or greater than a predetermined threshold(e.g., greater than 240 CEM) to form a lesion of a smallest volume thatstill achieves denervation (e.g., ablation) of 75% of the nerve branchesof a basivertebral nerve within a vertebral body. For example, thelesion zone may form a 1 cm diameter sphere that may be elongated oradjusted so as to achieve the 75% denervation depending on the vertebralbody characteristics (e.g., level, bone mass density, etc.). A majoraxis may be between 10 mm and 30 mm (e.g., between 10 mm and 20 mm,between 10 mm and 15 mm, between 15 mm and 25 mm, between 10 mm and 25mm, between 15 mm and 30 mm, overlapping ranges thereof or any valuewithin the recited ranges) and a minor axis may be between 5 mm and 20mm (e.g., between 5 mm and 10 mm, between 5 mm and 15 mm, between 8 mmand 15 mm, between 10 mm and 15 mm, between 15 mm and 20 mm, overlappingranges thereof, or any value within the recited ranges). A major axislength to minor axis length ratio may be between 1:1 and 5:1 (e.g.,between 1:1 and 2.5:1, between 1:1 and 2:1, between 1:1 and 3:1, between1.5:1 and 3:1, between 2:1 and 4:1, overlapping ranges thereof, or anyvalue within the recited ranges, such as 1.2:1, 1.8:1, 1.5:1, 2:1,2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, or 5:1).

The various treatment parameters described herein may be adjusted toeffect a desired lesion shape. FIGS. 5A-5D Illustrate various lesionshapes that may be generated by one or more treatment devices 712. Forexample, as shown in FIG. 5A, a desired lesion shape may befootball-shaped or elliptical-shaped to obtain more anterior-posteriorcoverage. In some implementations, medial-lateral coverage could besacrificed to obtain more anterior-posterior coverage. The desiredmaximum length (dimension of longer axis) and width (dimension ofshorter axis) of the football-shaped lesion may be, for example, 30mm×10 mm, 25 mm×10 mm, 20 mm×10 mm, 30 mm×15 mm, 25 mm×15 mm. In someimplementations, the football-shaped lesion has a maximum length tomaximum width ratio of about 1.8:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1,4.5:1, or 5:1. The lesion shape may be oval, elliptical (FIG. 5B),cigar-shaped or disc-shaped (FIG. 5C), UFO-shaped (FIG. 5D),rectangular, X-shaped, cross-shaped, or amorphous in variousembodiments.

Impedance may be monitored during energy delivery and if impedance isdeemed to be outside of a safety threshold range, the energy deliverymay be automatically terminated or an alert may be generated so as toprevent, or reduce the likelihood of occurrence of, charring. Highimpedance measurements may be triggered by increased blood flow in ornear the treatment region, thereby resulting in undesired stoppages orinterruptions in treatment even though these high impedance measurementsdo not present safety risks. In accordance with several implementationsinvolving radiofrequency energy delivery devices, detection of regionsof high blood flow in or near the target treatment region may beperformed in order to position the electrodes in a location that doesnot have high blood flow in order to avoid these undesired interruptionsin energy delivery once energy delivery is initiated. In addition, bloodflow may be detected and/or monitored during the treatment procedure andadjustments may be made to the energy delivery algorithm so as not toterminate or interrupt energy delivery when the “false positive” highimpedance measurements are obtained as a result of increased blood flow.Multiple thermocouples may be positioned along a length of a treatmentprobe to steer the treatment probe toward or away from locations of highblood flow.

For implementations involving two treatment probes, each treatment probecan include two or more electrodes and voltage differentials may beapplied between different pairs of electrodes on the two probes toadjust the shape of the lesion. The paired electrodes may vary or betoggled such that different pair combinations of electrodes are formedfor various durations of time in a predetermined pattern or based onfeedback from one or more sensors. The pairs of electrodes may includetwo electrodes on the same probe and/or two electrodes on differentprobes. In one implementation, a voltage differential may be appliedbetween electrodes of the same probes for a certain duration and thenthe voltage differential may be applied between electrode “pairs”disposed on different probes for a certain duration. The durations maybe the same or different, depending on the shape of the lesion desired.As an example of an implementation involving use of two probes eachhaving two electrodes, a distal electrode of a first probe may be pairedwith a distal electrode of a second probe and a proximal electrode ofthe first probe may be paired with a proximal electrode of the secondprobe for a first duration of time. Then, the distal electrode of thefirst probe may be paired with the proximal electrode of the secondprobe and the distal electrode of the second probe may be paired withthe proximal electrode of the first probe for a second duration of time.This pattern may be repeated multiple times over a total treatmentduration. The energy delivery devices (e.g., probes) may be connected toa single energy source (e.g., generator) or separate energy sources(e.g., generators).

The durations may vary as desired and/or required (e.g., 20 seconds to60 seconds, 30 seconds to 90 seconds, 45 seconds to 90 seconds, 1 minuteto 2 minutes, 90 seconds to 3 minutes, 2 minutes to 4 minutes, 3 minutesto 5 minutes, 4 minutes to 6 minutes, 6 minutes to 15 minutes,overlapping ranges thereof, or any value within the recited ranges). Thecorresponding pairs of electrodes may be switched or toggled as manytimes as desired to form different lesion patters and to adjust overalllesion shape.

Use of two devices or probes may advantageously form synergistic lesionsthat provide greater surface area or coverage (or the same amount ofcoverage or treatment efficacy but in a more efficient manner) thancould be achieved by independent lesions formed by the separate devicesor probes or by a single probe that is moved to different locations. Inaccordance with several embodiments, the use of two probes and switchingpatterns of energy delivery between pairs of electrodes mayadvantageously allow for replenishment of blood in the target treatmentregion to reduce impedance stoppages.

With reference to FIG. 6, in implementations involving two treatmentdevices or probes, the access tools may include two cannulas orintroducers 612 each having a radial, or lateral side, window 613 at itsdistal end and a curved or angled ramp 616 to guide a treatment probe617 (e.g., treatment device 312) inserted therethrough in a curved orangled direction upon exiting the radial window 613. The windows 613 ofthe two introducers 612 may be positioned to face toward each other sothat the treatment devices or probes 617 curve out of the radial windows613 toward each other to more effectively control lesion formation andshape as opposed to two probes simply being inserted straight in to thevertebral body (e.g., through separate pedicles). In someimplementations, the windows 613 of the introducers/cannulas 612 arevisible under fluoroscopy or CT imaging so as to facilitate positioningwithin a vertebral body or other bone. The introducers 612 may beinserted in combination with an introducer stylet transpedicularly orextrapedicularly into the vertebral body. The introducer stylets maythen be removed and the treatment devices or probes 617 then inserted.In some implementations, the introducers 612 have a sharp distal tip andintroducer stylets are not required. In some implementations, initialpaths are created through the cortical shell of the vertebral body by aseparate access instrument and then the introducers 612 are introducedinto the vertebral body.

Nerve detection and/or monitoring techniques may be performed duringinsertion of access tools or treatment devices to increase efficacyand/or targeting. Determined distances between the treatment device andtarget nerves may be used to adjust treatment parameters to increaseefficacy of the treatment. For example, if it is determined from thetechniques that a treatment device is in contact with a nerve or withina certain threshold distance from the nerve, ablation time duration maybe decreased. However, if it is determined from the nerve detectionand/or monitoring techniques that the treatment device (e.g., energydelivery device) is greater than a threshold distance away from thenerve, the ablation time duration may not change or may be increased.The distance between (or contact between) the treatment device and thetarget nerve may be monitored intra-procedurally and parameters may beadjusted in real time.

The nerve detection techniques may be performed by a laparoscopic device(e.g., catheter or probe with one or multiple stimulation and/or sensoryelectrodes). The device may be manually controlled or roboticallycontrolled (e.g., using a robotic system such as the robotic systemdescribed in connection with FIG. 7). The device may be in electricalcommunication with an analyzer unit programmed to analyze signals fromthe device to determine the proximity of the device to the nerve. Theanalyzer unit may be coupled to an output device (such as a speaker orvisual display with a graphical user interface) that is configured tooutput a quantitative or qualitative output indicative of proximity. Thequalitative output may comprise a change in intensity, frequency,volume, or sound of an audible output or a change in color correspondingto distance on a visual display. The quantitative output may compriseactual numeric values of distances displayed on a display screen (e.g.,display 408 of generator 400).

Lesion Formation Assessment

Lesion assessment may be performed in real-time during treatment toprovide confirmation of treatment or other feedback to a clinicianperforming the treatment. For example, real-time input of lesioncharacteristics or lesion formation (e.g., size, temperature, tissueviability, nerve conduction) may be monitored to assure coverage and/orefficacy. Such techniques may advantageously provide intraoperative,real-time confirmation of ablation. Lesion characteristics may beobtained from a variety of sensors (e.g., temperature sensors, impedancesensors) and/or from intra-procedural images.

In some implementations, infrared sensing techniques may be performed toconfirm that the treatment device is in a desired treatment locationwithin the vertebral body or other bone and providing sufficientcoverage to effect ablation of the basivertebral nerve or tumor withoutover-extending the coverage. For example, the lesion may be thermallymapped using multiple thermocouples (e.g., two, three, four, five, six,or more than six) positioned at different locations within the vertebralbody or other bone and calculations using bioheat transfer equations maybe performed by a computer or processor to transform the measurementsobtained from the multiple thermocouples into a graphical visualizationof the lesion shape or zone in real time (e.g., thermal map). Thegraphical visualization, or thermal map, may be generated and displayedon a graphical user interface of a display device (e.g., display 608 ofgenerator 600). Different colors may be used to represent differenttemperature ranges. The treatment procedure may be continued until thelesion reaches a certain desired size or shape as determined from thegraphical visualization. The graphical visualization may be sufficientlysized such that it can be overlaid on top of actual anatomical images ofthe vertebral body so as to facilitate determination of proper lesionformation sufficient to ablate the basivertebral nerve within thevertebral body.

In some implementations, heat markers (e.g., temperature-dependentindicators) may be added to the target treatment zone that under MR orCT imaging manifest in a different way so that a clinician can visualizethe lesion growing in real time. For example, once a particulartemperature has been reached and maintained for an amount of timesufficient to ensure ablation, the heat marker may appear differentlyunder imaging.

In other implementations, an ultrasound balloon catheter (e.g., having asensor/emitter combination) may be inserted through one of the pedicles(e.g., on a contralateral side) to map water density changes duringablation, which would be indicative of ablation, edema, etc.

In some implementations, a high-frequency emitter and multiplethermocouples may be used to generate a radar map of bone that can bedisplayed on a display device (e.g., of the radiofrequency generator).In some implementations, a closed loop system may be employed in which arobotic controller is actively moving a device that changesconfiguration (e.g., based on artificial intelligence feedback). Forexample, a probe may be driven to a preselected target using imaging andlive feedback.

In accordance with several implementations, biomarkers may be used toconfirm treatment efficacy (e.g., whether the procedure resulted ineffective ablation of a basivertebral nerve within a vertebral body oran intraosseous nerve within another bone and achieved a desirabletherapeutic response). Biomarkers can include anatomical, physiological,biochemical, molecular parameters or imaging features that can be usedto confirm treatment efficacy. Biomarkers can be detected and measuredby a variety of methods, including but not limited to, physicalexamination, laboratory assays (such as blood samples), and medicalimaging. Biomarkers may be obtained via biological tissue sampling or ina minimally invasive manner (e.g., from blood, saliva, cerebrospinalfluid, or urine). Tissue imaging may also be used to detect and measurebiomarkers. Biomarker levels (e.g., substance P or cytokine or heatshock protein levels) may be measured using various in vivo or in vitro(ex vivo) kits, systems, and techniques (e.g., radio-immunoassaykits/methods, enzyme-linked immunosorbent assay kits,immunohistochemistry techniques, array-based systems, bioassay kits, invivo injection of an anticytokine immunoglobulin, multiplexedfluorescent microsphere immune-assays, homogeneous time-resolvedfluorescence assays, bead-based techniques, interferometers, flowcytometry, etc.). Cytokine proteins may be measured directly orindirectly, such as by measuring mRNA transcripts.

The measurement of biomarker levels can utilize one or more capture ordetection agents that specifically bind to the biomarker, such as alabeled antibody to bind and detect a biomarker. In someimplementations, measurement of biomarkers may utilize a detection agentthat has a functional interaction with the biomarker. In otherimplementations, measurement of biomarkers may be carried out usingimaging/spectroscopy techniques that allow biomarkers levels to beassessed in a non-invasive manner or by tissue sampling. Capture ordetection agents may be used. In some implementations, binding of abiomarker to a capture agent and/or interaction of the biomarker with adetection agent results in a quantitative, or detectable, signal. Thesignal may include, for example, a colorimetric, fluorescent, heat,energy, or electric signal. The detectable, quantitative signal may betransmitted to an external output or monitoring device. In someimplementations, binding of a biomarker to a capture agent results in asignal that can be transmitted to an external monitoring device. Forexample, binding of a biomarker to a capture or detection agent may bedetected using a high sensitivity fluorescence technique such as aresonance energy transfer method (e.g., Forster resonance energytransfer, bioluminescence resonance energy transfer, or surface plasmonresonance energy transfer).

In various implementations, the measurement of pre- and post-treatmentbiomarker levels may be carried out using the same device that is usedto carry out the treatment (e.g., ablation, denervation) or a componentattached to the treatment device. Alternatively, biomarker level oractivity may be carried out using a separate device from the treatmentdevice. The separate biomarker assessment device may be inserted throughthe same introducer as the treatment device or a separate introducer.

Biomarkers may include genetic markers, products of gene expression,autoantibodies, cytokine/growth factors, proteins or enzymes (such asheat shock proteins), and/or acute phase reactants. Biomarkers mayinclude compounds correlated to back pain, such as inflammatorycytokines, Interleukin-1-beta (IL-1-beta), interleukin-1-alpha(IL-1-alpha), interleukin-6 (IL-6), IL-8, IL-10, IL-12, tumor necrosisfactor-alpha (TNF-alpha), granulocyte-macrophage colony stimulatingfactor (GM-CSF), interferon gamma (INF-gamma), and prostaglandin E2(PGE2). Biomarkers may also be indicative of presence of tumor cells ortissue if tumor tissue is being targeted by the treatment. Biomarkersmay be found in blood serum/plasma, urine, synovial fluid, tissuebiopsy, foramina, intervertebral discs, cerebrospinal fluid, or cellsfrom blood, fluid, lymph node, and/or tissue.

One or more samples, images, and/or measurements may be obtained from apatient prior to treatment and after treatment and the presence of oneor more biomarkers in the pre-treatment and post-treatment samples maybe compared to confirm treatment efficacy. The comparison may involvecomparison of levels or activity of the biomarkers within the samples.For example, there may be a burst or spike in biomarker concentrationfollowing ablation of the basivertebral nerve trunk or branches thereofthat can be detected or measured within a collected biological sample.

As another example, the change in the level or activity of thebiomarker(s) may be an indirect response to ablation of thebasivertebral nerve trunk or branches thereof (e.g., an inflammatory oranti-inflammatory protein, such as a cytokine protein, a heat shockprotein, or a stress response protein that is triggered in response toablative energy being applied to the target treatment region or anon-protein biomarker associated with nervous activity, such ascatecholamines, neurotransmitters, norepinephrine levels, neuropeptide Ylevels, epinephrine levels, and/or dopamine levels). The post-treatmentsamples may be obtained immediately following treatment (e.g., withinseconds after treatment, within about 15 minutes following treatment, orwithin about 30 minutes following treatment) and/or may be obtainedafter a more significant amount of time following treatment (e.g., 24hours after treatment, 3 days after treatment, 1 week after treatment, 2weeks after treatment, 1 month after treatment, 3 months aftertreatment, 6 months after treatment).

Brain imaging or monitoring of brain activity (e.g.,electroencephalography, magnetoencephalography) may also be used toconfirm efficacy of treatment. The brain imaging or monitoring may beused to determine perception of pain by the patient. Such imaging and/ortemperature and/or impedance measurements may also be used incombination with, or as an alternative to, biomarkers to assess lesionformation or confirmation of denervation. Various inputs (e.g.,biomarker activity or levels, physiological parameter measurementsindicative of neuronal activity, temperature measurements, impedancemeasurements, and/or images), may be combined (e.g., weightedcombinations) to generate a quantitative pain score that can be used toconfirm pain relief (as an adjunct or as an alternative to subjectivepain relief confirmation). The pain score may be generated using anautomated algorithm executed by a processor of a pain analyzer system.The pain analyzer system may receive input from various sensors, imagingdevices, and/or the like and the input may be weighted and/or processedby one or more circuits or processing modules of the pain analyzersystem to generate the quantitative pain score. The quantitative painscore may be output on a display (e.g., of a generator).

Robotically-Assisted Access and/or Treatment

Access to and/or treatment within or adjacent bones (e.g., vertebralbodies) may be facilitated by the use of robotic navigation systems orrobotically-controlled devices (e.g., computer-aided orcomputer-assisted systems or devices). For example, robotics may be usedto facilitate or assist in positioning, targeting, deployment (e.g.,hammering) so as to avoid over-insertion that might cause injury ordamage, and/or to facilitate nerve sensing. FIG. 7 schematicallyillustrates an example of a robotically-enabled system 700. The roboticsystem 700 may be a robotic control, surgical, and/or navigation systemcapable of performing a variety of medical and/or diagnostic proceduresand/or providing guidance and enhanced imaging to a clinician. Therobotic system 700 may be a robotic assisted spinal surgery system, or aspinal robotics system.

The robotic system 700 may include an operator workstation or controlconsole 702 from which a clinician can control movement of one or morerobotic arms 703 to provide improved ease of use and fine control ofmovement. The workstation or control console 702 may include acomputer-based control system that stores and is configured to execute(e.g., using one or more processors) program instructions stored on anon-transitory computer-readable storage medium (e.g., solid statestorage drive, magnetic storage drive, other memory).

The robotic arms 703 may be configured to move with six or more degreesof freedom and to support or carry the access tools, treatment devices,and/or diagnostic devices. The robotic arms 703 may be coupled to asupport system and controlled by one or more instrument drive systemsthat are in turn controlled by the control console 702. The instrumentdrive systems may include electro-mechanical components and mechanisms(e.g., gears, pulleys, joints, hydraulics, wires, etc.) configured toactuate and move the robotic arms 703.

The robotic system 700 may also include one or more imaging devices 704(cameras, endoscopes, laparoscopes, ultrasound imaging modality,fluoroscopic imaging modality, MR imaging modality, and/or the like).The imaging devices 704 may be supported or carried by one or more ofthe robotic arms 703. The imaging devices 704 may be components of animaging system that facilitates 360-degree scanning of a patient. Theimaging devices 704 may include stereotactic cameras and/orelectromagnetic field sensors. In some implementations, the imagingdevices 704 of the robotic system 700 reduce an amount of patientexposure to radiation. The imaging devices 704 may be calibrated topatient anatomy or using reference pins or trackers positioned at one ormore locations of the patient's body by a registration, or localization,system. The registration system may include multiple computing devices(e.g., processors and computer-readable memory for storing instructionsto be executed by the processor(s)). The registration may involveidentification of natural landmarks of one or more vertebrae (e.g.,using a pointer device or the registration system).

The imaging system may be configured to communicate with software (e.g.,running on the operator workstation or control console 702 or theregistration system) that is configured to generate a real-time 3D mapthat may be registered with the robotic arms 703 or instruments carriedby the robotic arms 703. The software may include surgery planningsoftware configured to plan, based on pre-operative images (e.g.,obtained via CT, MRI, fluoroscopy, or other imaging modalities) adesired trajectory for access to a target treatment location within avertebral body or other bone. However, pre-operative planning may not beused in some implementations and navigation may be performedintraoperatively. The software may include navigation softwareconfigured to control the robotic arms 703 and provide feedbackregarding navigation (e.g., trajectory and positioning information) toan operator at the operator workstation or on a separate display device.A computing device of the control console 702 is configured to directmovement of the robotic arms 703 based on instructions executed by thecomputing device (either via inputs (e.g., joystick controls) from aclinician or via automated programs and artificial intelligencealgorithms stored in memory). The computing device includes one or morespecialized processors. The robotic system 700 may be used to carry outany of the methods of access, diagnosis, or treatment described hereinwhile providing controlled movements to reduce likelihood of injurycaused by manual operator error or error in judgment.

In some implementations, the robotic system 700 includes a closed-loopsystem that alters trajectory of access tools or treatment devices basedon feedback (e.g., artificial intelligence). The neuromodulation mayalso be robotically implemented based on intelligent (e.g., artificialintelligence) feedback. The robotic system 700 may include amachine-driven navigation system deploying an energy source towards atarget within a vertebral body to be treated. Detection and monitoringof the energy source's proximity to the target may be provided by theone or more imaging devices. The robotic system 700 can independentlymodify the trajectory in response to imaging or other registrationmodalities. Modification of the trajectory may be via change in theconfiguration of a driving system (e.g., robotic arms 703) and/or bychange of the configuration of the energy delivery device or assembly.Modification of trajectory may be automatic (e.g., closed-loop) or basedon a feedback mechanism to an operator (e.g., open-loop). The open-loopmode may include boundary conditions (e.g., haptic conditions) or not.The detection and monitoring functions may rely on pre-operative and/orintra-operative data. Registration and targeting may be a priori orinteractive.

CONCLUSION

In some implementations, the system comprises various features that arepresent as single features (as opposed to multiple features). Forexample, in one embodiment, the system includes a single radiofrequencygenerator, a single introducer cannula with a single stylet, a singleradiofrequency energy delivery device or probe, and a single bipolarpair of electrodes. A single thermocouple (or other means for measuringtemperature) may also be included. Multiple features or components areprovided in alternate embodiments.

In some implementations, the system comprises one or more of thefollowing: means for tissue modulation (e.g., an ablation or other typeof modulation catheter or delivery device), means for monitoringtemperature (e.g., thermocouple, thermistor, infrared sensor), means forimaging (e.g., MRI, CT, fluoroscopy), means for accessing (e.g.,introducer assembly, curved cannulas, drills, curettes), etc.

Although certain embodiments and examples have been described herein,aspects of the methods and devices shown and described in the presentdisclosure may be differently combined and/or modified to form stillfurther embodiments. Additionally, the methods described herein may bepracticed using any device suitable for performing the recited steps.Further, the disclosure (including the figures) herein of any particularfeature, aspect, method, property, characteristic, quality, attribute,element, or the like in connection with various embodiments can be usedin all other embodiments set forth herein. The section headings usedherein are merely provided to enhance readability and are not intendedto limit the scope of the embodiments disclosed in a particular sectionto the features or elements disclosed in that section.

While the embodiments are susceptible to various modifications, andalternative forms, specific examples thereof have been shown in thedrawings and are herein described in detail. It should be understood,however, that the embodiments are not to be limited to the particularforms or methods disclosed, but to the contrary, the embodiments are tocover all modifications, equivalents, and alternatives falling withinthe spirit and scope of the various embodiments described and theappended claims. Any methods disclosed herein need not be performed inthe order recited. The methods disclosed herein include certain actionstaken by a practitioner; however, they can also include any third-partyinstruction of those actions, either expressly or by implication. Forexample, actions such as “applying thermal energy” include “instructingthe applying of thermal energy.”

The terms “top,” “bottom,” “first,” “second,” “upper,” “lower,”“height,” “width,” “length,” “end,” “side,” “horizontal,” “vertical,”and similar terms may be used herein; it should be understood that theseterms have reference only to the structures shown in the figures and areutilized only to facilitate describing embodiments of the disclosure.The terms “proximal” and “distal” are opposite directional terms. Forexample, the distal end of a device or component is the end of thecomponent that is furthest from the operator during ordinary use. Adistal end or tip does not necessarily mean an extreme distal terminus.The proximal end refers to the opposite end, or the end nearest theoperator during ordinary use. Various embodiments of the disclosure havebeen presented in a range format. It should be understood that thedescription in range format is merely for convenience and brevity andshould not be construed as an inflexible limitation on the scope of theinvention. The ranges disclosed herein encompass any and all overlap,sub-ranges, and combinations thereof, as well as individual numericalvalues within that range. For example, description of a range such asfrom 70 to 115 degrees should be considered to have specificallydisclosed subranges such as from 70 to 80 degrees, from 70 to 100degrees, from 70 to 110 degrees, from 80 to 100 degrees etc., as well asindividual numbers within that range, for example, 70, 80, 90, 95, 100,70.5, 90.5 and any whole and partial increments therebetween. Languagesuch as “up to,” “at least,” “greater than,” “less than,” “between,” andthe like includes the number recited. Numbers preceded by a term such as“about” or “approximately” include the recited numbers. For example,“about 2:1” includes “2:1.” For example, the terms “approximately”,“about”, and “substantially” as used herein represent an amount close tothe stated amount that still performs a desired function or achieves adesired result.

What is claimed is:
 1. An introducer system adapted to facilitate percutaneous access to a target treatment location within bone, the introducer system comprising: an introducer cannula comprising a proximal handle and a distal elongate hypotube extending from the proximal handle; and an introducer stylet comprising a proximal handle and a distal elongate shaft extending from the proximal handle, wherein the proximal handle of the introducer cannula comprises a central opening in its upper surface that is coupled to a lumen of the distal elongate hypotube to facilitate insertion of the introducer stylet into the central opening and into the distal elongate hypotube, wherein the proximal handle of the introducer cannula comprises one or more slots configured to receive at least a portion of the proximal handle of the introducer stylet so as to facilitate engagement and alignment between the introducer stylet and the introducer cannula, wherein at least one of the one or more slots is in communication with the central opening of the proximal handle of the introducer cannula, wherein the proximal handle of the introducer stylet comprises an anti-rotation tab configured to be received within one of the one or more slots so as to prevent rotation of the introducer stylet within the introducer cannula, wherein a distal end of the distal elongate shaft of the introducer stylet comprises a distal cutting tip and a scalloped section proximal to the distal cutting tip so as to provide gaps between an outer diameter of the distal end of the distal elongate shaft and the inner diameter of the introducer cannula, and wherein the proximal handle of the introducer stylet further comprises a press button that, when pressed: (a) disengages the anti-rotation tab and allows for rotation of the introducer stylet within the introducer cannula, and (b) allows for removal of the introducer stylet from the introducer cannula.
 2. The introducer system of claim 1: wherein the press button is integrally coupled to the anti-rotation tab, wherein the scalloped section gradually tapers from a full diameter proximal portion to a narrow-most middle portion and then gradually tapers back to a full diameter distal portion, and wherein the proximal handle of the introducer cannula comprises a T-shaped design.
 3. The introducer system of claim 1, further comprising a curved cannula assembly, the curved cannula assembly comprising: a cannula comprising a proximal handle with a curved insertion slot and a distal polymeric tube, wherein the distal polymeric tube comprises a curved distal end portion having a preformed curvature but configured to bend when placed under constraint; a stylet comprising a proximal handle and a distal elongate shaft, wherein the distal elongate shaft comprises: a curved distal end portion having a preformed curvature but configured to bend when placed under constraint and a distal channeling tip.
 4. The introducer system of claim 1, further comprising an introducer drill adapted to be introduced into and through the introducer cannula to form a further path within the bone after removal of the introducer stylet from the introducer cannula.
 5. The introducer system of claim 4, wherein the introducer drill comprises a fluted distal portion and a distal drill tip.
 6. The introducer system of claim 5, wherein drill flutes of the fluted distal portion taper away from the distal drill tip so as to facilitate bone chip packing within an open volume defined by the drill flutes as bone chips are generated by operation of the introducer drill.
 7. The introducer system of claim 1, wherein the scalloped section comprises a plurality of grooves sized to hold bone debris.
 8. The introducer system of claim 1, wherein the at least one of the one or more slots is a curved insertion slot.
 9. An introducer system adapted to facilitate percutaneous access to a target treatment location within bone, the introducer system comprising: an introducer cannula comprising a proximal handle and a distal elongate hypotube extending from the proximal handle; and an introducer stylet comprising a proximal handle and a distal elongate shaft extending from the proximal handle, wherein the proximal handle of the introducer cannula comprises a central opening in its upper surface that is coupled to a lumen of the distal elongate hypotube to facilitate insertion of the introducer stylet into the central opening and into the distal elongate hypotube, wherein the proximal handle of the introducer cannula comprises one or more slots configured to receive at least a portion of the proximal handle of the introducer stylet so as to facilitate engagement and alignment between the introducer stylet and the introducer cannula, wherein at least one of the one or more slots is in communication with the central opening of the proximal handle of the introducer cannula, wherein the proximal handle of the introducer stylet comprises an anti-rotation tab configured to be received within one of the one or more slots so as to prevent rotation of the introducer stylet within the introducer cannula, wherein a distal end of the distal elongate shaft of the introducer stylet comprises a distal cutting tip and a scalloped section proximal to the distal cutting tip so as to provide gaps between an outer diameter of the distal end of the distal elongate shaft and the inner diameter of the introducer cannula.
 10. The introducer system of claim 9: wherein the scalloped section gradually tapers from a full diameter proximal portion to a narrow-most middle portion and then gradually tapers back to a full diameter distal portion, wherein the proximal handle of the introducer stylet comprises a ramp configured to provide a mechanical assist for removal of the introducer stylet from the introducer cannula; and wherein the proximal handle of the introducer cannula comprises a T-shaped design.
 11. The introducer system of claim 9, wherein the scalloped section gradually tapers from a full diameter proximal portion to a narrow-most middle portion and then gradually tapers back to a full diameter distal portion.
 12. The introducer of claim 11, wherein the taper is symmetric.
 13. The introducer system of claim 9, wherein the scalloped section comprises multiple scallops sized to hold bone debris.
 14. The introducer system of claim 9, wherein the scalloped section comprises a side profile having an hourglass shape.
 15. The introducer system of claim 9, wherein the press button is integrally coupled to the anti-rotation tab such that pressing of the press button extends the anti-rotation tab out of a constraint of the one or more slots.
 16. The introducer system of claim 9, wherein a length of the distal elongate shaft is between 8 mm and 14 mm.
 17. An introducer system adapted to facilitate percutaneous access to a target treatment location within bone, the introducer system comprising: an introducer cannula comprising a proximal handle and a distal elongate hypotube extending from the proximal handle; and an introducer stylet comprising a proximal handle and a distal elongate shaft extending from the proximal handle, wherein the proximal handle of the introducer cannula comprises a central opening in its upper surface that is coupled to a lumen of the distal elongate hypotube to facilitate insertion of the introducer stylet into the central opening and into the distal elongate hypotube, wherein the proximal handle of the introducer cannula comprises one or more slots configured to receive at least a portion of the proximal handle of the introducer stylet so as to facilitate engagement and alignment between the introducer stylet and the introducer cannula, wherein at least one of the one or more slots is in communication with the central opening of the proximal handle of the introducer cannula, and wherein the proximal handle of the introducer stylet comprises an anti-rotation tab configured to be received within one of the one or more slots so as to prevent rotation of the introducer stylet within the introducer cannula.
 18. The introducer system of claim 17, wherein the proximal handle of the introducer stylet further comprises a press button that, when pressed: (a) disengages the anti-rotation tab and allows for rotation of the introducer stylet within the introducer cannula, and (b) allows for removal of the introducer stylet from the introducer cannula.
 19. The introducer system of claim 17, wherein the press button is integrally coupled to the anti-rotation tab such that pressing of the press button extends the anti-rotation tab out of a constraint of the one or more slots.
 20. The introducer system of claim 17, wherein a length of the distal elongate shaft is between 8 mm and 14 mm.
 21. The introducer system of claim 17, wherein the proximal handle of the introducer stylet comprises a ramp configured to provide a mechanical assist for removal of the introducer stylet from the introducer cannula. 